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Nick from Bakersfield

by @ ImmInst Active Topics

Greetings all!

 

My Name is Nick, and like the title states, I am from Bakersfield California. I've lurked around the forums here for quite some time, and my primary interest is in the area of nutrition and supplementation/nootropics. I have a little experience, primarily with Piracetam and Choline supplementation, but am looking to broaden my horizons so to speak. Anyways, just wanted to introduce myself and thank everyone in advance for their advice and contributions!

 

Regards,

Nick

Supplement Review: Nicotinamide Riboside

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Nootropics in human trials (Intro)

by @ Articles - Articles

The word "nootropic" derives from the Greek words nous, or "mind", and trepein meaning "to bend or turn". It was first coined by Romanian psychologist and chemist, Corneliu E. Giurgea after synthesizing Piracetam.
For Giurgea a nootropic drug should have the following characteristics:
1. They should enhance learning and memory.
2. They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3. They should protect the brain against various physical or chemical injuries (e.g. barbiturates, scopalamine).
4. They should increase the efficacy of the tonic cortical/subcortical control mechanisms.
5. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

In fact, most drugs commonly labelled as nootropics do not fulfill all of these requirements. Some of the best known (e.g. Adderall, Modafinil) seem to not fulfill any, as discussed later. Instead, other characteristics like (reputed increased alertness, focus or motivation) seem to be key to their popularity.
Because of deviating definitions nootropics are more broadly defined (e.g. in wikipedia) as drugs, supplements, or other substances that improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals. 

Some nootropics from the very common to the :

Caffeine
Caffeine is the world’s most widely used stimulant (Nawrot, et al., 2003). It is used by over 90 % of North Americans every day (Mednick et al., 2008). It is widely used because of its positive effects on mood and alertness (Lorist & Tops, 2003)and vigilance and attention (Lieberman et al., 1987). However, these effects do not seem applicable / transferable to motor learning and verbal memory and are unable to reverse effects of sleep deprivation, with a dose of 200mg in low to moderate users (< than 2 cups a day) (Mednick et al., 2008). It is also shown to be ineffective in higher cognitive tasks involving working memory (Battig et al., 1984). Overall conclusions regarding the relation of caffeine and memory have been mixed. Positive effects might stem from caffeine withdrawal in high dosage users (Mednick et al., 2008).

Nicotine
With about 1,1 billion smokers worldwide in the year 2015 (WHO 2015) nicotine takes second place as the most widely used stimulant. It was shown that the application of nicotine in non-smoking males enhances performance in continuous performance tasks and therefore is said to improve attention and working-memory (Kumari, et al., 2003), which is in line with other studies suggesting that nicotine affects short-term memory in delayed free recall tasks (Sarah & Fox, 1998)
Another study examined nicotine’s effects on alertness and performance on a covert orienting task were measured. While nicotine decreased overall reaction times in the covert orienting task, there was no change in the validity effect, the reaction time difference between validly and invalidly cued targets. However, nicotine significantly improved both EEG and self-rated measures of alertness. Nicotine seems to increases alertness in non-smokers, with no improvement in spatial attention using a covert orienting task (Griesar et al., 2002). Furthermore Nicotine seems to reduce distraction under low perceptual load by acting as a stimulus filter that prevents irrelevant stimuli entering awareness (Behler et al., 2015).

Methylphenidate/ Ritalin
Most college students I know will immediately think of Ritalin or Modafinil if they are asked to name a cognitive enhancer. Studies have found that 4.1% to 10.8% of college students in the US reported using prescription stimulants non-medically during the past year (Garnier-Dykstra, et al., 2012).
Methylphenidate (MPH - common brand name ‘Ritalin’) is used in treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Most studies focused on the its effects on Attention, Mood, Memory and executive functions. A single dose of MPH showed a positive effect on memory. Repeated doses of MPH had a mood elevating effect but also enhanced anxiety. No statistically significant effect was found in the outcomes attention, mood and executive functions. MPH had no significant effect on sleep-deprived individuals (Repantis et al., 2010). In a 2015 review the authors found some ‘publication bias’, relating to long-term and working memory and conclude that the effect in healthy subject is probably modest overall and that healthy users resort to stimulants to enhance their energy and motivation more than their cognition (Ilieva et al., 2015). 

Modafinil
Modafinil is used in treatment of disorders such as narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Most studies focused on its effects on attention, mood, memory, wakefulness and executive functions and motivation. A single dose showed positive effects on attention only. On sleep deprived individuals it was shown to have an impact on executive functions, on memory and wakefulness but there was an insignificant effect on mood and attention (Repantis et al., 2010). A 2012 meta-analysis found that Modafinil was likely effective but criticised the gaps in the literature. (Kelley et al., 2012) 
A recent study on chess players found significantly enhanced performance with Modafinil or Ritalin but only when the players were not under time pressure (Franke et al. 2017). 

Adderall
Mixed Amphetamine Salts also known under the brand Name Adderall became increasingly popular in recent years as an athletic performance enhancer and cognitive enhancer. Like Ritalin, it is also used to treat ADHD and narcolepsy.
Overall effects of Adderall on cognition have been reviewed as very modest, while having a huge effect on perception. It was found to enhance performance in word recall, embedded figures and Raven's Progressive Matrices, but only for lower performing individuals (Ilieva et al., 2013). Adderall might also impair creativity in high performing individuals (Farah et al., 2009).

L-theanine & Caffeine
L- theanine is primarily found in plants (e.g. in the leaves of green and black tea) and fungus. Results evidently demonstrated that L-theanine clearly has a pronounced effect on attention performance and reaction time response in normal healthy subjects susceptible to having high anxiety (Higashiyama et al., 2011).
A dose of L-theanine equivalent to eight cups of black tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. The combination of Theanine and caffeine seem to have additive effects on attention in high doses (Kahathuduwa et al.,2016).
Studies suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task (Giesbrecht 2010).

Bacopa Monnieri
Bacopa Monnieri is an herb which has been used in Ayurvedic medicine for centuries. Bacopa's primary mechanism of action is still unclear, it seems to be an anti-oxidant, a weak acetylcholinesterase inhibitor and a cerebral blood flow activator (Aguiar & Borowski , 2013).
There is some evidence to suggest that Bacopa Monnieri improves memory with little evidence of enhancement in any other cognitive domains (Pase et al., 2012).

Piracetam
Closing the circle to the beginning of this short introduction to the topic: Giurgea first coined the term "nootropic" when he synthesized Piracetam in 1964. Since it is not approved by the US FDA, it is primarily used in Europe, Asia, and South America. It is commonly prescribed for cognitive impairment and dementia in several countries of Europe. Research suggests that Piracetam might also have a positive effect on healthy individuals. Subjects were given 3×4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased (Dimond & Brouwers, 1976). It might also be beneficial for cognitive decline associated with age. Aging subjects did significantly better in a computerized perceptual-motor tasks when on piracetam than on a placebo. (Mindus et al. 1976). While these old studies may not be that reliable, it is still held that Piracetam's “efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated” (Winblad, 2005). Since Piracetam was first synthesized many structurally similar compounds have emerged. These so called Racetams have poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems (Gualtieri et al., 2002).


This article is solely for information purposes, not a substitute for professional medical or dietary advice. 
The provisos of the LongeCity user agreement apply.

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References
* Aguiar, S., & Borowski , T. (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research, 313-326. 
* Battig , K., Martin, J. R., & Feierabend , J. M. (1984). The effects of caffeine on physiological functions and mental performance. Experentia, 1218–1223.
* Behler , O., Breckel, T. P., & Thiel , C. M. (2015). Nicotine reduces distraction under low perceptual load. Psychopharmacology, 1269-1277.
* Dimond, S. J., & Brouwers, E. M. (1976). Increase in the power of human memory in normal man through the use of drugs. Psychopharmacology, 307-309.
* Farah , M., Haimm , C., Sankoorikal , G., Smith , M., & Chatterjee , A. (2009). When we enhance cognition with Adderall, do we sacrifice creativity? A preliminary study. Psychopharmacology,541-547.
* Franke, A.G.; Gränsmark, P., Agricola, A., Schühle, K., Rommel, T., Sebastian, A., Balló, H.E., Gorbulev, S., Gerdes, C., Frank, B., Ruckes, C., Tüscher, O., Lieb, K. (2017) "Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial" in: European Neuropsychopharmacology Vol27, Issue 3, 1, pp248-260
* Garnier-Dykstra, L. M., Caldeira, K. M., Vincent, K. B., O’Grady, K. E., & Arria, A. M. (2012).Nonmedical use of prescription stimulants during college: Four-year trends in exposure opportunity, use, motives, and sources. J Am Coll Health, 226-234.
* Giesbrecht, T., Rycroft , J. A., Rowson , M. J., & De Bruin , E. A. (2010). The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutritional Neuroscience, 283-290.
* Griesar , W. S., Zajdel , D. P., & Oken , B. (2002). Nicotine effects on alertness and spatial attention in non-smokers. Nicotine & Tobacco Research, 185-194.
* Gualtieri , F., Manetti , D., Romanelli , M. N., & Ghelardini , C. (2002). Design and study of piracetamlike nootropics, controversial members of the problematic class of cognition-enhancing drugs. Current Pharmaceutical Design, 125-138.
* Higashiyama, A., Htay, H. H., Ozeki, M., Juneja, L. R., & Kapoor, M. P. (2011). Effects of l-theanine on attention and reaction time response. Journal of Functional Foods, 171-178.
* Ilieva, I., Boland, J., & Farah, M. (2013). Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people. Neuropharmacology, 496-505.
* Ilieva IP, Hook CJ, Farah MJ. (2015) Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis.; J Cogn Neurosci. 2015 Jun;27(6):1069-89. 
* Kahathuduwa, C. N., Dassanayake , T. L., Amarakoon , A. M., & Weerasinghe, V. S. (2016). Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutritional Neuroscience.
* Kelley, A.M.; Webb, C.M., Athy, J.R., Ley, S., Gaydos, S. (2012) "Cognition enhancement by modafinil: A meta-analysis" in Aviation Space and Environmental Medicine; Vol83, Issue 7, p685-690
* Kumari, V., Gray, J., H ffytche, D., Mitterschiffthaler, M., Das, M., Zachariah, E., . . . Sharma, T. (2003). Cognitive effects of nicotine in humans: an fMRI study. NeuroImage, 1002-1013.
* Lieberman , H. R., Wurtman, R. J., Emde, G. G., Roberts , C., & Coviella, I. L. (1987). The effects of low doses of caffeine on human performance and mood. Psychopharmacology, 308-312.
* Lorist , M. M., & Tops, M. (2003). Caffeine, fatigue, and cognition. Brain Cognition, 82-94.
* Mednick, S. C., Cai, D. J., Kanady, J., & Drummond, S. P. (2008). Comparing the benefits of Caffeine,Naps and Placebo on Verbal, Motor and Perceptual Memory. Behavioural Brain Research, 79–86.
* Mindus , P., Cronholm , B., Levander , S. E., & Schalling , D. (1976). Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. Acta Psychiatrica Scandinavia, 150-160.
* Nawrot, P., Jordan, S., Eastwood , J., Rotstein , J., Hugenholtz, A., & Feeley, M. (2003). Effects of caffeine on human health. Food Additives & Contaminants, 1-30.
* Pase, M. P., Kean , J., Sarris , J., Neale , C., Scholey , A. B., & Stough , C. (2012). The cognitive enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. Journal of Alternative Complementary Medicine, 647-652.
* Repantis , D., Schlattmann , P., Laisney , O., & Heuser, I. (2010). Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacological Research, 187-206.
* Sarah , P., & Fox, P. (1998). An investigation into the effects of nicotine gum on short-term memory.Psychopharmacology, 429-433.
* WHO (2015). WHO global report on trends in tobacco smoking 2000-2025. WHO Library Cataloguing-in Publication Data .
* Winblad, B. (2005). Piracetam: a review of pharmacological properties and clinical uses. CNS Drug reviews, 169-182.

Probiotic Yeast Vs Bacteria Poultry

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Post lyme disease treatment advice...diet, bpc 157 and or?

by @ Health

Hey everyone,

Thank you in advance for taking the time to read and respond to my post. I’m a 23 year old (otherwise healthy) male who was diagnosed with lyme disease about two months ago. After undergoing an intense supplement/herbal/energetical therapy cleanse and detox, my docotor confirmed that the lyme had left my body. However, I am still experiencing all of my original symptoms, including random shaking, a neck tremor, intense brain fog, a really infammed gut/liver/kidneys, etc. I’m struggling to determine my next course of action — has anyone reading his post dealt with lyme? — have you tried dietary changes to help heal your system? I’m also curious if bpc 157 would be a good option for me? I already eat a fairly well balanced diet that is exclusively organic/non gmo, as well as taking about 15 relevant supplents a day (including probiotics). I guess, in general, I’m seeking any lyme, dietary, or other advice that you might have for me.

Thanks for your time,

-Braden

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Cryonics

by @ Articles - Articles

The following is a quick overview on Cryonics.

 

NB: The information below is periodically reviewed for accuracy, but LongeCity makes no representations or gives any warranties whatsoever that the following information is accurate and complete at any point in time. LongeCity accepts no responsibility or liability for information contained on this page. The discussion of cryonics service providers and services in no way entails any endorsement on part of LongeCity. The lead author of this page, its editors and other contributors from time to time may be affiliated with one of the service providers mentioned below. Without qualification to the foregoing disclaimers, LongeCity strives to present the following information in an objective and balanced manner. If you feel that information on this page is inaccurate or imbalanced please contact the LongeCity Support Email.

 

INDEX

Cryonics Overview

 

Cryonics is based on the idea that future medicine will have capabilities well beyond those of current medicine, including the ability to cure all diseases, rejuvenate and repair damage incurred in the cryopreservation process — through the use of nanotechnology and other technologies. Cryonics can be an ambulance or time capsule to future medicine which can allow us to live many thousands of years or longer in youth and good health. Stored at very low temperatures there will be very little molecular motion in cryonics patients for tens of thousands of years, although most of us do not believe that we will have to wait anywhere near so long for future medicine.

 

Although cryonics patients must be legally dead before cryonics procedures to reduce or eliminate ischemic damage and ice formation can be applied, cryonicists do not believe that cryonics patients are dead in an ultimate sense. Nearly all the cells of the body are alive for quite some time after the heart stops — including neurons. A standby team can be used to minimize the time between pronouncement of death and cooling, cardiopulmonary support, etc. Cryonicists believe that the anatomical basis of mind can survive much longer than six minutes after stoppage of the heart in the absence of cooling — despite the inability of current medicine to revive patients without neurological damage after more than six minutes of cardiac arrest. (See Quantifying Ischemic Damage for Cryonics Rescue for more details.)

 

Existing Cryonics Organizations

 

For most of cryonics history (which began in the mid-1960s), all of the cryonics organizations offering cryonics services have been in the United States. In 2005 a cryonics organization was created in Russia (just northwest of Moscow) and there are plans for another cryonics organization in Australia to offer perfusion and storage of cryonics patients within a few years. LongeCity does not endorse any particular cryonics organization. The data below is taken from the cryonics organizations without LongeCity attempting to verify the accuracy of their claims or the extent of the services they claim to provide. If you are considering utilizing any of these organizations, you should conduct your own investigation.

 

NAMELOCATIONINCORPORATEDNON-PROFIT ?
Alcor Life Extension FoundationScottsdale, Arizona1972Yes
American Cryonics Society (ACS)Cupertino, California1969Yes
Cryonics Institute (CI) Clinton Township, Michigan1976Yes
KrioRus Moscow, Russia2005No
Oregon Cryonics Salem, Oregon2005*No
Suspended Animation, Inc (SA) Boynton Beach, Florida2002No
Trans Time, Inc.San Leandro, California1972No

 

Alcor Life Extension Foundation and the American Cryonics Society (ACS) are organized as 501©3 charitable organizations, whereas the Cryonics Institute (CI) is simply a non-profit corporation. Although Suspended Animation, Inc. (SA) is ostensibly a for-profit company, it is mainly engaged in research and development of cryonics capabilities financed by the principals of the Life Extension Foundation. By 2012 KrioRus had relocated to a facility closer to Moscow, but a newer facility is being built midway between Moscow and St. Petersburg.

 

Oregon Cryonics was incorporated in 2005, but accepted its first patient (a pet patient) in May, 2014. Jordan Sparks is the owner/operator, but he has plans for a Board of Directors or other mechanism to out-live him (to allow for the organization to continue).

 

Cryonics Services Offered

 

Not all cryonics services are offered by all cryonics organizations. Patient administration service is offered by cryonics organizations that sign-up Members who are to be cryopreserved upon legal death and maintain responsibility for those Members while they are Patient's in cryopreservation storage. Perfusion is the replacement of normal body fluid with cryoprotective solutions to reduce or prevent ice formation at cryogenic temperatures. Storage is the storage of a cryonics patient in liquid nitrogen. Standby/Stabilization/Transport (SST) involves standing by the bedside of a medically terminal patient destined to be cryopreserved, the application of a heart-lung resuscitator and ice-water cooling as soon as possible after declaration of death,and transport to a perfusion facility while tissues are still being stabilized at low temperature.

 

The following table represents the services which cryonics organizations say they provide.

 

NAMEPATIENT ADMINISTRATIONPERFUSIONSTORAGESST
AlcorYesYesYesYes
ACSYesYes*No*Yes*
CIYesYesYesNo*
KrioRusYesYesYesNo
Oregon CryonicsYesYesYesNo
SANo*NoNoYes
Trans TimeYesNoYesNo
*=simplification, see explanation

 

All standby cases done for Alcor Foundation outside of Arizona, but inside the continental United States are handled by Suspended Animation, Inc (SA). Alcor does standby for Alcor Members who are terminal in Arizona, Hawaii, and Alaska as well as in Canada. SA does not provide SST services outside the continental United States for any organization.

 

The American Cryonics Society (ACS) states that it mainly contracts with Suspended Animation,Inc. (SA) for perfusion and standby/transport, and contracts with the Cryonics Institute (CI) for storage. ACS also states that it has equipment, contractors and volunteers which are available for use in perfusion and standby in California should the need arise, although this is far less sophisticated and formal than what SA provides. ACS creates and manages individual charitable trusts for its patients. ACS regards these trusts as an important feature of the benefit gained by being an ACS Member.

 

Cryonics Institute (CI) Members who reside in the continental United States have the option of contracting directly with SA if they desire professional SST.In some cases volunteers or paid funeral directors have provided these services to CI Members. SA will keep records of CI Members who have arranged to have SA SST, but does not continue any administrative responsibility after the patient has been cryopreserved.

 

Trans Time is currently storing patients, but (despite what their website says) is not currently seeking new Members or Patients.

 

Sizes of the Organizations

 

There are various ways by which organization size could be measured, but for the purposes of this section size is represented by the number of Members in the organization, the number of patients currently being stored in liquid nitrogen and the number of full-time paid staff in the organization. The figures below are for April 2017, and are based on the statements of the organization in question.

 

NAMEMEMBERSFUNDED MEMBERSPATIENTSSTAFF
Alcor1,639*1,132*1509*
ACS?*?*20*1*
CI1,384*?*151*3*
KrioRusN/AN/A527*
Oregon Cryonics8*N/A65*
SAN/AN/AN/A3*
Trans Time??31?
*=simplification, see explanation

 

The Membership statistics reported above are for living Members only. Both Alcor and CI patients are Members (except for the ACS patients at CI). The American Cryonics Society (ACS) has an organizational policy against publishing the number of Members it has in its organization. As of April 2017 the 20 ACS patients were all in storage at the Cryonics Institute (CI). ACS has had one part-time clerk to do office work and has otherwise relied on volunteers. Alcor has 9 full-time staff, 1 consultant, and 1 regular volunteer. The 151 patients in storage at CI includes 20 ACS patients. KrioRus has no Membership program, and the method of counting patients is odd — a few are not stored by KrioRus. KrioRus has 4 full-time and 3 part-time employees as well as numerous volunteers.

 

CI is a subcontractor for storage of 20 ACS patients. CI has three paid staff (two full-time and one part-time), a few contractors and many volunteers. Accounting is done by CI Treasurer Pat Heller (a CPA) with auditing by another CI Director. Trans Time does not report its Membership numbers. Suspended Animation (SA) is a subcontractor which provides Standby/Stabilization/Transport (SST) only to other cryonics organizations (ACS, Alcor and CI), so it has no Members or Patients — so the reporting of Members or Patients for SA is "Not Applicable" (N/A). SA makes extensive use of subcontractors when needed.

 

As of April 2017, CI reported 136 pets, Alcor reported 58 pets, KrioRus reported 21 pets, and Oregon Cryonics reported 2 pets in cryopreservation.

 

Alcor and CI member numbers are not directly comparable because the word "Member" has different meanings for the two organizations. Membership in CI provides the privilege of obtaining cryopreservation services: pet, DNA or human cryopreservation. Many join CI only to store DNA or pets or to support CI, including some Alcor Members. Some Alcor Members have even made arrangements to use CI as a "back-up". Alcor does not allow its Members to have Alcor as a "back-up". Prior to April, 2012, all Alcor Members had made arrangements (ie, funding and contracts in place) for human cryopreservation and SST, but in April 2012 the Associate Alcor Member program was introduced. Associate Alcor Members do not have any cryopreservation arrangements with Alcor.

 

ForApril 2017, Alcor reported 1,639 living Members, 1,132 of whom had made arrangements for human cryopreservation, and 357 of whom were Associate Members. Of the 1,384 CI Members in April 2017, 212 of those had made arrangements for both human cryopreservation and standby/stabilization/transport (all with SA). In September 2015, CI ceased reporting how many of it Members have funding and contracts for cryopreservation. Historically, less than half of CI Members have been funded (prior CI statistics). Since 2006, CI offers a 'partnership' arrangement for CI Members for SA SST.

 

As noted in the previous section, Trans Time is currently storing patients, but (despite what their website says) is not currently seeking new Members or Patients.

 

In 2011 and 2012 SA reorganized its staff to have more part-time employees and contractors, and for much of 2012 and 2013 SA was re-organizing to have facilities in both California and Florida.

 

Oregon Cryonics has an owner (Jordan Sparks) and four other full-time employees. OC has 9 Members, but is no longer accepting new Members..

 

Accounts of patient histories and membership growth can be found at:
--Cryonics Institute (CI) Patient Details
--Cryonics Institute (CI) Statistics Details
--Complete List of Alcor Cryopreservations
--Alcor Membership Statistics

 

Whole Body/Neuro Options

 

The term neuropreservation (or "neuro") generally refers to the practice of cryopreserving only the head rather than the whole body. A "neuro" is usually a whole head, not just the brain, but sometimes only the brain is cryopreserved. Keeping the whole head to preserve the brain is convenient for both perfusion and storage (the skull protects the brain). In some cases, however, "neuros" are brain-only. The following represent options various organizations say that they offer.

 

NAMEWHOLE BODYNEURO
AlcorYesYes
ACSYesNo*
CIYesNo
KrioRusYesYes
Oregon CryonicsNoYes
SAN/AN/A
Trans TimeYesYes
*=simplification, see explanation

 

Alcor states that its Members have the option of having their whole body cryopreserved or only their head ("neuro") — with different fees applicable to each choice. In April 2017, Alcor reported having 93 neuro, 54 whole body, and 4 neuro+whole bodypatients, whereas KrioRus reported 25 neuro and 27 whole-body patients. Trans Time has one whole body and two brains.

 

All CI Members with human cryopreservation arrangments are "whole body". ACS states that it does not have a policy against neuropreservation, but as long as it only uses CI as its subcontract or for storage it cannot offer neuro-cryopreservation as an option. Suspended Animation (SA) is a subcontractor which provides Standby/Stabilization/Transport only to other cryonics organizations, not storage, so the question of storage options with SA is "Not Applicable" (N/A).

 

Oregon Cryonics only stores heads and brains. As of February, 2016 Oregon Cryonics was chemically preserving three human brains, and cryopreserving one dog brain.

 

Cryopreservation and Yearly Fees

 

Comparing fees for human cryopreservation and yearly Membership or Emergency Responsibility is difficult to summarize in table form because the policies, procedures and options between the cryonics organization are so different. A great deal of explanation is required. Note that the high prices for human cryopreservation are generally covered by life insurance policies. The following represent the fees that the following organizations state that they charge.

 

NAMEWHOLE BODYNEUROYEARLY FEES
Alcor$200,000*$80,000*$620*
ACS$155,000*N/A$376*
CI$28,000*N/A$120*
KrioRus$36,000*$12,000None
Oregon CryonicsN/A$25,000*None
SAN/AN/ANone
Trans Time$150,000$50,000$96*
*=simplification,see explanation

To Alcor's yearly fee of $620 annual dues, those living in the United States and Canada must add $180 yearly SST fees for a total of $800 per year. A lifetime payment plan is also available. SST service is not available to Alcor Members outside of the US and Canada, but a $15,000 surcharge is added to whole body and neuro prices in the United Kingdom, and a $25,000 surcharge is added to the prices paid by those living in other countries. For details on Alcor pricing, see Schedule A: Required Costs and Suspension Funding Minimums.

 

The prices given for the American Cryonics Society (ACS) are intended to reflect comparable service to what Alcor provides. In fact, ACS has a very wide menu of options and prices available, including reference to a "California Procedure" which is intended to be distinguished from the"Michigan Procedure" offered by the Cryonics Institute. The yearly fee for an ACS Member is $376 for the first four years and $300 per year thereafter. For details on ACS options and fees, see:www.americancryonics.org.

 

The Cryonics Institute (CI) charges $28,000 for perfusion and storage of a Lifetime Member and $35,000 for a Yearly Member. These prices do not include funeral director costs or shipment to CI for non-local cases. (When CI was begun it was imagined that every state would have at least one cryonics service provider.) The Lifetime CI Member has paid a one-time $1,250 fee and the Yearly CI Member has paid a $75 initiation fee and is paying a $120 yearly fee. Discounts for additional family members and underage family members apply only to Lifetime Memberships. For service more comparable to what Alcor provides — including Standby/Stabilization/Transport (SST) — a Lifetime Member pays $88,000 and a Yearly Member pays $95,000. For details on CI pricing see Membership andDetails Concerning SA Standby and Transport for CI Members.

 

For $49,000 KrioRus states that it offers Russians (Europeans?) the option of shipment and storage at the Cryonics Institute in the USA.

 

Oregon Cryonics charges $25,000 to cryopreserve a whole head, $18,000 for a brain with braincase, and $14,000 for a brain without the braincase. Oregon Cryonics will chemically preserve a brain for as little as $1,000 (see Oregon Cryonics Service Fees for details).

 

As noted in previous sections, Trans Time is currently storing patients, but (despite what their website says) is not currently seeking new Members or Patients.

 

Suspended Animation (SA) is a subcontractor which provides SST only to other cryonics organizations, not Membership or storage, so the question of these options with SA is "Not Applicable" (N/A).

 

Human Cryopreservation Procedures

 

Human cryopreservation procedures are much too complex to be summarized effectively here.

 

Alcor's procedures are summarized on a page of the Alcor website called Alcor Procedures. But is it also very helpful to read actual case reports of Alcor patients in the Cryopreservation Case Reports section of the Alcor website library.

 

CI has a summary of its procedures on its website calledGuide to Cryonics Procedures. CI procedures do not include Standby/Stabilization/Transport (SST), though CI will advise Members on obtaining assistance through local funeral directors. CI Members residing in the continental United States who wish to obtain SST can do so by subcontracting with Suspended Animation, Inc. (SA).

 

Although the American Cryonics Society (ACS) has equipment and volunteers which could be used if necessary, ACS basically relies on SA for Standby/Transport and CI for Perfusion/Storage.The human cryopreservation procedures of Trans Time and KrioRus are not documented on their websites.

 

Funding Cryonics by Insurance
The cost of cryonics is many thousands of dollars, but most cryonicists cover these costs with life insurance policies that name a cryonics organization as beneficiary. Premiums of life insurance policies are most affordable for those who are young and healthy. It is not prudent to seek life insurance in old age or after a terminal illness (when life insurance may be unobtainable). Nor is it prudent to believe that cryonics arrangements can be made efficiently or successfully when in a terminal condition.

 

Rudi Hoffman sells the great majority of cryonics life insurance policies. It makes good sense to take advantage of Rudi's considerable expertise in matters of cryonics and life insurance. (A sincere and unpaid plug for Rudi.)

I am running a Rapamycin, Rifampicin and Allantoin cycle

by @ ImmInst Active Topics

mTor, JNK, AMPK, IGF-1/Calorie Restriction seem to be the four major routes that most supplements and drugs that have been shown to extend lifespan work through.  A few months ago it was shown that Rapa, Rifa and Allantoin could consistenlty double the lifespan of flies and c.elegans.  (Here is the full study: https://www.biorxiv.org/content/biorxiv/early/2017/06/21/153205.full.pdf) 

 

Most of us that have been watching longevity animal studies over the years have noticed that when researchers add two or more drugs that are known to extend lifespan independently, the end result is often a decrease in lifespan.  The authors above noted that this phenomenon is likely caused by adding supplements with mechanical overlap/working through the same pathway which ends up negating each other's activity.  Therefore, they identified these three supplements to work on all four of these pathways with minimal overlap.  

 

So I am running Rapamycin at 1-2mg a week, Rifampicin at 150mg once every three days, and Allantoin through comfrey root with the harmful chemicals extracted.  I have dropped Metformin, which has unimpressive results with Rapa in multiple studies.  The only other supplements I will be taking are spermidine (which has been shown to have up to a 20% increase in mouse lifespan) and resveratrol (which works synergistically with spermidine on different pathways to promote autophagy).  I rotate these into the regime after the Rapa is out of my system, because Rapa also promotes autophagy.  I also rotate in Sulforphane Glucosinolate (Brocco Max) with NR to increase AMPK twice a week.  I try to add in some glycine from time to time, which was shown to increase rodent lifespan up to 40% but, it may overlap with the other CR mimetics (Allantoin and Rapa) so I use it when those two are not in my system.    

 

Thus far the only thing I have noticed is a surprising boost of energy about an hour after taking the Rifampicin and lasting several hours onward.  I am going to be taking periodic liver functions tests to make sure the Rifa isn't causing any hepatotoxic problems.  I will let you all know if anything comes of this, but I believe this regime is probably just about the best one available given the information we have thus far on longevity.  

Hi, there. new guy on the block

by @ ImmInst Active Topics

I'm 71 YO.  trying to out run mother nature with exercise, diet and enjoy it more with occasional use of mainly stimulatory, legal supplements.  I mainly use phenylpiracetam, piracetam, coffee.  I am a master's level psychologist (industrial/organizational by occupation).  Retired from that an now teach 5 Intro, Child psych classes at several 2 year colleges in southern New Jersey.

My fitness routine involves resistance work and sprinting.

Chapmans Probiotic Frozen Yogurt Cancer Prostate Colorectal Cancer

by @ Probiotics Belaw

As it turns out probiotics provide daily Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Kettlewell MG Colorectal cancer and benign tumors of the colon. Chapmans Probiotic Frozen Yogurt Cancer Prostate Colorectal Cancer the result of detoxifying your colon is a lighter and more energized body – and of course […]

When Should I Take a Probiotic If I’m on Antibiotics?

by Linda Agin @ Bottom Line Inc

QI am taking an antibiotic for an infection, and I want to take a probiotic as well to protect my stomach. Should I take it during or after my course of antibiotics? AYou should absolutely take a probiotic supplement—and you’re right to ask about timing. Antibiotics can upset the balance of beneficial bacteria in your [...]

The post When Should I Take a Probiotic If I’m on Antibiotics? appeared first on Bottom Line Inc.

Do Probiotics Help With Mood Plants

by @ Probiotics Belaw

Rich Shewmaker <rich@ilhawaii.net> wrote or quoted: > I challenge anyone to probiotics for reptiles activity lactobacillus come up with a single report of a Answering The Question: How Does Sea Salt Cleanse The Colon? Hydrotherapy Colon Cleanse Is Far Superior A Method Than Enema. Do Probiotics Help With Mood Plants what makes matters even worse […]

Beet Kvass – GAPS Approved

by Becky Plotner @ Nourishing Plot

Beet kvass is a probiotic drink so common in the country of Moldova that there are kvass vending machines on city streets. You put your coin in the machine, pick your kvass flavor and the machine squirts your flavored kvass into a glass sitting on a shelf in the middle of the machine. [...]

The post Beet Kvass – GAPS Approved appeared first on Nourishing Plot.

Nccn Colon And Rectal Cancer Guidelines Are Made Poop

by @ projectathena probiotics composition

Prebiotics in food contribute to enhance the growth and maintain the viability of probiotics. Nccn Colon And Rectal Cancer Guidelines Are Made Poop does probiotics help you lose weight? This is still up for debate. OSLO?Pregnant women who regularly consume probiotic-rich milk or yogurt have a reduced risk of developing preeclampsia according to a new […]

My Favorite Post-Workout Supplements to Speed Muscle Recovery

by Holly Lucille, ND, RN @ Bottom Line Inc

Whether you hike, do strength training or intense Crossfit classes, here are my favorite supplements to keep up my energy and ensure a quick recovery.

The post My Favorite Post-Workout Supplements to Speed Muscle Recovery appeared first on Bottom Line Inc.

Checkout 51 Cash Back Offers (Feb 15 - 21)

by couponlady @ SmartCanucks.ca Flyers, Deals Canada

Attachment 338970 (https://forum.smartcanucks.ca/attachments/canadian-shopping-deals-flyers/338970-checkout-51-cash-back-offers-feb-15-21-1.jpg) New offers will go live at 12:00 AM February 15, 2018, and...

Rectal Bleeding Prostate Cancer Loss Kefir Weight Plan

by @ Probiotics Belaw

You can learn about probiotic supplements and Probiotics NZ can advise you how to take them. Rectal Bleeding Prostate Cancer Loss Kefir Weight Plan hospitals offering this leading-edge procedure. Probiotic not as the products. Use NOW Immune Renew to help support healthy immune function throughout the year.* NOW Immune Renew delivers the natural nutrient profile […]

Probiotics Yogurt For Ibs Intolerance Milk Lactose

by @ Probiotics Belaw

Die off can also occur perpetually. AVI-CULTURE-2 is the NUMBER ONE all-natural live 10-strain avian-specific Non-GMO Dairy-Free FOS-Free & Allergen-Free Now the new & improved AVI-CULTURE-2 surpasses that making IT the best avian-specific probiotic for all birds on the planet! Up to 75 percent of women will have a yeast infection in their lifetime and […]

Mitochondrially Targeted Antioxidant SS-31 Improves Cognitive Function in Old Mice

by @ LongeCityNews

Oxidative damage has long been linked to aging, but the general use of antioxidants does nothing for life span. In fact, the evidence suggests this approach is modestly harmful, possibly due to blocking the oxidative signaling needed for exercise and other, similar mild stresses to produce benefits via hormesis. Antioxidant compounds targeted to the mitochondria are a different story, however, and have been shown to slow aging or partially reverse some aspects of aging in mice and lower animals - as is the case in this open access paper.

Mitochondria are the power plants of the cell, and generate reactive molecules that raise oxidative stress as a side-effect of the processes that produce chemical energy stores. This flow of reactive molecules influences the behavior of the cell in numerous ways; methods of slightly slowing aging have been demonstrated that either lower production, leading to less oxidative damage, or raise it, spurring increased maintenance activities in the cell. In the research here, benefits are derived indirectly: damping down oxidative damage improves the function of blood vessels in the aged brain, which helps to restore some degree of lost cognitive function in old mice. The brain is an energy-hungry organ, and age-related neurodegenerative conditions are characterized by a general decline in the capacity of of the blood supply and mitochondria in cells to supply as much energy as is needed.

Normal functioning of the central nervous system (CNS) requires a continuous, tightly controlled supply of oxygen and nutrients as well as washout of harmful metabolites through uninterrupted cerebral blood flow (CBF). The energetic demands of neurons are very high, yet the brain has very little energetic reserves. During periods of intense neuronal activity, there is a requirement for adjusting oxygen and glucose delivery to local neuronal activity through rapid adaptive increases in CBF. This is ensured by a mechanism known as neurovascular coupling (NVC). The resultant functional hyperemia is a vital mechanism to maintain optimal microenvironment of cerebral tissue and thereby ensuring normal neuronal function.

There is an increasing appreciation that (micro)vascular contributions to cognitive impairment and dementia in elderly patients are critical. Importantly, neurovascular coupling responses are impaired both in elderly patients and aged laboratory animals. Experimental studies support this concept, showing that pharmacologically induced neurovascular uncoupling in mice mimics important aspects of age-related cognitive impairment. On the basis of these findings, we proposed that novel therapeutic interventions should be developed to rescue functional hyperemia in elderly patients to prevent/delay cognitive impairment. Previous studies demonstrate that aging exacerbates generation of reactive oxygen species (ROS) in the cerebromicrovascular endothelial cells, which contribute to age-related neurovascular uncoupling in aged mice by promoting endothelial dysfunction. We hypothesize that pharmacological treatments, which attenuate endothelial oxidative stress, will have the capacity to improve neurovascular coupling in aged individuals.

The mitochondrial free radical theory of aging posits that mitochondria-derived ROS (mtROS) production and related mitochondrial dysfunction are a critical driving force in the aging process. In support of this theory, it was demonstrated that attenuation of mitochondrial oxidative stress (by mitochondria-targeted overexpression of catalase) increases mouse lifespan. There is particularly strong evidence that mitochondrial oxidative stress is implicated in cardiovascular aging processes. Yet, although drugs that improve mitochondrial function have been shown to exert beneficial effects both on the vasomotor function of peripheral arteries, their potential protective effects on the aged cerebral microvasculature has not been investigated.

This study was designed to test the hypothesis that pharmacological attenuation of mtROS can restore cerebromicrovascular endothelial function and thus improve neurovascular coupling in aged mice. To achieve this goal, in aged mice mitochondrial oxidative stress was manipulated by treatment with the mitochondrial-targeted peptide SS-31. We found that neurovascular coupling responses were significantly impaired in aged mice. Treatment with SS-31 significantly improved neurovascular coupling responses by increasing cerebromicrovascular dilation, which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination. These findings are paralleled by the protective effects of SS-31 on mitochondrial production of reactive oxygen species and mitochondrial respiration in cultured cerebromicrovascular endothelial cells derived from aged animals.

Link: https://doi.org/10.1111/acel.12731


View the full article at FightAging

LongeCityNow_Neil_Thanedar_2017.mp3

by @ Last 10 Submissions RSS Feed

Listen in and find out how Labdoor is helping the supplement industry. Are your supplements, safe, pure, and accurately labeled?

Costco Executive Coupons - Save Money in Winnipeg

Costco Executive Coupons - Save Money in Winnipeg


Save Money in Winnipeg

The new Costco Executive coupons are out. These are only valid if you have an Executive membership, and they’re good from April 18th to May 1st 2016. There’s actually 2 booklets this time – one is the regular one with $66 in savings, the other is a Kirkland Signature Savings booklet – again only for …

Fermented Fish, The Perfect Travel Food – GAPS Approved

by Becky Plotner @ Nourishing Plot

Fermented fish provides a plethora of probiotic strains.

Nutrients says, “Lactic acid bacteria (LAB) consist of homo and hetero-lactic acid organisms, and are a broad category of bacteria, including Lactobacillus, Streptococcus, Enterococcus, Lactococcus and Bifidobacterium, with the ability to produce lactate primarily from sugars. They are among the most commercially used bacteria [...]

The post Fermented Fish, The Perfect Travel Food – GAPS Approved appeared first on Nourishing Plot.

Supplement Development - Great results as of late

by @ LONGECITY Community Blog List

I've been using a bunch of supplements and improvised materials that just haven't been done yet and have been getting great results. Then two nights ago I add a half dose of an adjuvant to my existing regimen that can slowly remove glucosepane, or so it seems. I have it on good authority that this mechanism will be effective. The new ingredient is working wonders. After I shaved this morning, my face felt smoother than it had in years (I change my blades very infrequently, this one is at least a few months old and the disposable battery is about a month). The over all appearance of my skin has improved greatly in the last few weeks. At this point it looks like a pointalism painter painted some younger spots on my skin in layers and the layering is continuing. Interestingly enough, I was out walking about in the sun and overcast skies at a nearby college for several hours yesterday and was expecting my skin to look worse. I do take 4 supplements to minimize the effect of the sun on my skin as I have a somewhat mild (in cosmetic terms... medically it's atypical, basically I have a high enough adrenaline response to deal with the inflammation rapidly and systemically so I feel the effects differently and only get a few zits and a spell of anxiety) case of polymorphic light eruptions or what I refer to as sun sensitivity. The supplements virtually ameliorate the sensitivity most of the time.

 

Anyways, my skin got much better, though it was perhaps a little red and more wrinkled in areas such as that between my thumbs and pointer fingers, and I was exhausted by the end of the day. The skin returned to normal when the inflammation subsided.

 

I feel like we're getting real close for those of us who are informed enough to start defeating aging on our own.

Topical Probiotics For Diaper Rash High Are Potassium

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The herbs used in curing this may cause it just gets worse and worse because nothing helps food move more quickly can cause severe pain and colon cancer hepatic flexure COM X-RAY PATIENT POSITIONING MANUAL HTTP://XRAY.AUNTMINNIE.COM best rated live probiotics cramps help menstrual DIGITAL X-RAY A R T I C L E S Proper positioning […]

Costco Unadvertised Deals of the week starting Feb. 5th

by Nadine @ Save Money in Winnipeg

Lots of good deals at Costco this week, here they are from the Regent location in Winnipeg. Most will be the same store to store. Items ending in .97 are markdowns and are store specific. A lot of items with stars on them today which means they’re on their way out. If you ever see […]

The post Costco Unadvertised Deals of the week starting Feb. 5th appeared first on Save Money in Winnipeg.

Hi

by @ ImmInst Active Topics

Hello forum,

   I'm 38 and line in Southern California. Supplements I take right now are:

Morning - 1 Pill Resveracel, 1 Pill Crucera-SGS, 1 Scoop BHB Salt, 1 Scoopt MCT Oil, & Veggie Smoothie (or sub spirulena pills)

Nightime - 1 Pill Meriva-SF, Glucosamine (Thorne)

My goal is to stay physically healthy as long as possible. I'm pretty tall, and we don't seem to last as long. 

Right now I'm interested in Fullerene. 

Dr Ohhira Probiotics Uk Multi Effects Side Strain

by @ Probiotics Belaw

Today in History – Tuesday – July 31 2012 1792 – The cornerstone of the U.S. Most children with constipation do not have an underlying medical problem (such as low thyroid or a bowel anatomic abnormality) however if a consumer lab probiotic report homeopathic child has persistent Untie the tea towel from the wooden spoon. […]

Supplement Review: Nicotinamide Riboside

by @ Articles - Articles





Watch Out for Probiotics from Costco and Others | Bottom Line Inc

Watch Out for Probiotics from Costco and Others | Bottom Line Inc


Bottom Line Inc

Bottom Line/HEALTH: Is there a best probiotic that you recommend for people to take? Andrew Rubman, ND: Well, “recommend” meaning that I’

Probiotic Tablets Brands Pros

by @ projectathena probiotics composition

Culturelle Kids Probiotic Packets are a naturally sourced (especially for little ones) Flavorless so you can add to any cool liquid or food; Based on a 2012 survey among pediatricians recommending a probiotic and. Probiotic Tablets Brands Pros icd 9 colon cancer with mets PDF results. complete probiotic guide you will learn everything you would […]

Costco Weekly Coupons

by Nadine @ Save Money in Winnipeg

Lots of coupons starting today at Costco – you can get them instore or check them out online. There’s $4.50 off Cracker Barrel cheese slices, $3 off Zavida coffee, $4 off Purex, $5 off Tide, $18 off Canon ink cartridges, $100 off queen mattress and many more! And check back in later today for the […]

The post Costco Weekly Coupons appeared first on Save Money in Winnipeg.

Advertising Framework

by @ LongeCity - Articles

Visitors to the forum will notice that a lot of discussion evolves around nutrition, supplements and lifestyle. We realize of course that these factors are just one element of the larger mission to conquer the blight of involuntary death, but that makes it all the more important to make sure that the strengths that LongeCity has in providing a great resource for nutritional information exchange are leveraged effectively. 

Sometimes, it may seem like there are two 'factions' at LongeCity: on the one hand the committed 'activists' who realize the truth that nutritional supplements by themselves will have very limited efficacy in extending the human lifespan and who consequently have little patience  for 'supplement pushers'. On the other hand there are the 'supplementers' who have little to no interest in 'living forever' and whose priority is a healthy lifespan and enhancing their fitness. For sure, examples of both 'camps' can be found if one looks for them, but on the whole the distinction has very little merit: firstly, nutrition, drugs, vitamins and lifestyle - even apparently peripheral topics like cognitive enhancement, are an important factor in the portfolio of life extension technologies. These are the factors that we can do for ourselves, today and for that reasons alone are worth discussing. 

This fact- that supplements are at the 'applied' end of life extension discussion also means that the information and expertise joining at LongeCity around supplements can be much more effectively leveraged for fundraising. This makes LongeCity pretty unique: we are trying to siphon some of the financial overheads from the commercial end of life extension and re-allocate them to chronically underfunded scientific research and advocacy programmes. LongeCity has been really successful in this regard: with very little funding we have made a real difference in creating pioneering information material and funding important basic research as well as supporting community projects. 

Thus 'activists' can appreciate a measure of advertising at the sitefor making an important contribution to the common cause. Ad exposure for Members is reduced but not fully eliminated not least because we think that some ads can actually be useful and interesting. There are at least four types of  advertising available: 

'Google ads' - are context-related ads. Google offers these individually based on your browser's settings and the content of the forum. Consequently please bear in mind that LongeCity has very limited control about what ads are displayed.

'Banner ads' - these paid for adverts usually leading to a sponsors website. More about LongeCity's relationship with other institutions can be found in this article. To quote: "LongeCity does not endorse any advertisers beyond the fact that they have made a donation to the community in exchange for exposure. Advertisers never influence our policy, ever. (...) Having said that, advertisers featured at LongeCity very often have a real commitment to the cause- they would not have found us otherwise". Members are invited to comment on the policy

'Links' - these are links in text and elsewhere that are monetized if the link is used to make a purchase at the external site. One well known example is Amazon.com: If you use the LongeCity 'referral' page to make a purchase, Amazon makes a small payment to LongeCity at no cost to you. We may be experimenting with other link concepts in the future. Note however, that the connections on our links page are not used in this manner. They are simply a project index interesting sources that all members can contribute to. 

'Ads by discussion' - sometimes advertising momentum is generated simply by discussing a particular product. Over the years, marketers have become very sophisticated in pursuing such 'viral' strategies - and they are generally NOT WELCOME at LongeCity. There are only two sub-forums where product-and vendor related discussions are tolerated: for supplement companies/ for other companies. Any attempts to initiate product-related discussions elsewhere will be considered a breach of the LongeCity user agreement. The limited discussion that is allowed in this context is tolerated only because we feel that some information exchange about products and providers is potentially part of the LongeCity mission. Where this link cannot be made clearly, ads by discussion -whether inadvertent or not- will not be permitted.

We have experimented a little bit and are always keen to find other ways to generate funding for life extension research and advocacy from the LongeCity website in a way that is not overly intrusive and that does not compromise our mission and values. 
Potential sponsors are invited to get in touch. 
Members with new ideas about are invited to share them in the suggestions forum

Why do some turtles outlive humans?

by @ Articles - Articles

(⇒ write for LongeCity )


The oldest human recorded in modernity was Jeanne Louise Calment, she died in the age of 122 years and 164 days [1] .

There are rumors that the oldest tortoise called Adwaita (Aldabra giant tortoise) died in the age of about 250 years [2] or that it was 188-year-old radiated tortoise named Tui Malila [3] , or that the highest verified age of 177 years had Galapagos giant tortoise Harriet [4] . The oldest currently living turtle is considered to be Jonathan (Seychelles giant tortoise), estimated to be over 180 years old these days [5] . Although all aforementioned numbers are estimations, it seems these turtles were older than human supercentenarians.

All previously mentioned species are terrestrial tortoises, a group with longest lifespans among turtles. The most famous of them, well-researched Galapagos giant tortoise, was observed by Charles Darwin when he was forming his well-known theory of evolution by natural selection [6] . There is only one freshwater turtle known to be able to outlive human, it is the common snapping turtle estimated to live up to more than hundred years [7] . While being considerably less researched, recorded maximal lifespan of sea turtles is usually shorter, not exceeding 80 years, however, it is believed that the green sea turtle can live up to 100 years. [8]

It is a difficult question to answer why these reptiles can outlive us because even to determine the actual age of animals with a long lifespan is complicated – partially due to the fact that it takes such a long time to study. Furthermore, many turtles are endangered species [9] so there may not be as many organisms to hand as needed for proper statistics. Nonetheless, we can still claim that turtles are among the most long-living vertebrates on earth [10] . Why?

Firstly, turtles, like all reptiles, benefit from being ectothermic organisms. They do not maintain body temperature and thus save a lot of energy. But that also means they are less flexible: it is crucial for their lifespan to be in natural temperature environment of daily cycles with night-time temperature drop [11] . If they do not live under these conditions in captivity, metabolic pathways change and turtles die much sooner. [12]

Turtles are well-adapted in other ways: their famous shell – the carapace –is good protection against natural predators. Most of hatchling turtles with a soft shell do not survive the first year [13] . A research of natural populations of freshwater turtles showed that only one per cent of them can celebrate the twentieth birthdays, but once the adulthood is reached, mortality rate drops and remains constant throughout the rest of life [14] .

Some turtles can survive under extreme environmental conditions, such as freezing [15] or lack of oxygen for months [16] . They can even undergo hibernation and anaerobic metabolism and therefore deal with hypoxia and anoxia, it was also proposed that the same genes can play a role in longevity itself [17] and also in oxidative stress resistance [18] that further promotes longer life [19] .

Turtle’s bones and shell are used as lactate buffer lowering metabolic acidosis caused by anaerobic glycolysis during the period of lack of oxygen [20] ; [21] Their organism is protected by strong innate immunity compensating slow acquired immune reactions [22] .

Because turtles have very slow metabolism as well as growth, their bodies do not need to deal with excessive metabolic heat and byproducts as mammals [23] . Their natural diet is very simple but also necessary for their longevity. [24]

According to the evolutionary theories, staying alive is less important after menopause. Galapagos giant tortoises achieve sexual maturity late (around the age of up to forty years in the wild, and between twenty and twenty-five years of life in captivity [25] ), then staying fertile until death [26] .

The Hayflick limit is said to determine how many times a cell can divide [27] . The Hayflick limit of Galapagos giant tortoise was said to be about 110 divisions [28] , approximately twice as many as 50 of human cells [29] . Studies in this context have highlighted the importance of telomeres, the protective end sequences of chromosomes, that get shorter with each cell division [30] , can play at least a partially role in life expectancy. It was observed that telomeres in European freshwater turtle’s cells are of the same length in both embryo and adult organism [31] .

Thus, it was believed that turtles are negligibly senescent organisms [32] . In other words, the cells do not age and no age-related diseases appear, which is very different cell behavior than in human bodies [33] and probably the key to any natural longevity. However, evidence now suggests that turtles may not be really negligibly senescent because of observations of survival and reproductive senescence in late age in the painted turtle population [34]

As we can see, turtles have some advantages in the lifespan field. Some of these might inspire researchers to increase lifespans in humans.



References

[1] Oldest person ever. Retrieved January 31, 2017, from http://www.guinnessworldrecords.com/world-records/oldest-person
[2] BBC (2006, March 23). “Clive of India’s” tortoise dies. BBC South Asia. Retrieved from http://news.bbc.co.uk/2/hi/south_asia/4837988.stm
[3] Associated Press (2006, June 26). Tortoise believed to have been owned by Darwin Dies at 176. Fox News. Retrieved from http://www.foxnews.com/story/2006/06/26/tortoise-believed-to-have-been-owned-by-darwin-dies-at-176.html
[4] Galapagos tortoise (Geochelone nigra) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Geochelone_nigra
[5] Hollins, J. (2012). The world’s most isolated vet? Veterinary Record, 171(2), i–i. doi:10.1136/vr.g7292
[6] Powell, J., & Caccone, A. (2006). Giant tortoises. Current Biology, 16(5), R144–R145. doi:10.1016/j.cub.2006.02.050
[7] Cameron, M. (2008). COSEWIC Assessment and Status Report on the Snapping Turtle Chelydra serpentina in Canada . Retrieved from http://publications.gc.ca/collections/collection_2009/ec/CW69-14-565-2009E.pdf
[8] Green sea turtle (Chelonia mydas) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Chelonia_mydas
[9] Jacobson, E. R. (1994). Causes of Mortality and Diseases in Tortoises: A Review. Journal of Zoo and Wildlife Medicine, 25(1), 2–17.
[10] Gibbons, J. W. (1987). Why do turtles live so long? BioScience, 37(4), 262–269. doi:10.2307/1310589
[11] Flouris, A. D., & Piantoni, C. (2014). Links between thermoregulation and aging in endotherms and ectotherms. Temperature, 2(1), 73–85. doi:10.4161/23328940.2014.989793
[12] Vadala, N. How Long Do Turtles Live? Retrieved January 31, 2017, from http://www.petmd.com/reptile/care/how-long-do-turtles-live
[13] Stewart, K. R., & Wyneken, J. (2004). Predation risk to loggerhead hatchlings at a high-density nesting beach in Southeast Florida. Bulletin of Marine Science, 74(2), 325–335.
[14] Gibbons, J. W., & Semlitsch, R. D. (1982). Survivorship and longevity of a long-lived vertebrate species: How long do turtles live? The Journal of Animal Ecology, 51(2), 523. doi:10.2307/3981
[15] Packard, G. C., & Packard, M. J. (2003). Natural freeze-tolerance in hatchling painted turtles? Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 134(2), 233–246. doi:10.1016/s1095-6433(02)00264-7
[16] Milton, S. L., & Prentice, H. M. (2007). Beyond anoxia: The physiology of metabolic downregulation and recovery in the anoxia-tolerant turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 147(2), 277–290. doi:10.1016/j.cbpa.2006.08.041
[17] Shaffer, H. B., Minx, P., Warren, D. E., Shedlock, A. M., Thomson, R. C., Valenzuela, N., … Wilson, R. K. (2013). The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage. Genome Biology, 14(3), R28.doi:10.1186/gb-2013-14-3-r28
[18] Garbarino, V. R., Orr, M. E., Rodriguez, K. A., & Buffenstein, R. (2015). Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates. Archives of Biochemistry and Biophysics, 576, 8–16. doi:10.1016/j.abb.2015.01.029
[19] von Zglinicki, T. (2002). Oxidative stress shortens telomeres. Trends in Biochemical Sciences, 27(7), 339–344. doi:10.1016/s0968-0004(02)02110-2
[20] Jackson, D. C. (2000). Living without oxygen: Lessons from the freshwater turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 125(3), 299–315. doi:10.1016/s1095-6433(00)00160-4
[21] Krivoruchko & Storey, 2010).
[22] Sandmeier, F. C., Tracy, C. R., Dupre, S., & Hunter, K. (2012). A trade-off between natural and acquired antibody production in a reptile: Implications for long-term resistance to disease. Biology Open, 1(11), 1078–1082. doi:10.1242/bio.20122527
[23] Bilinski, T., Paszkiewicz, T., & Zadrag-Tecza, R. (2015). Energy excess is the main cause of accelerated aging of mammals. Oncotarget, 6(15), 12909–12919. doi:10.18632/oncotarget.4271
[24] Casares, M., Honegger, R. E., & Rubel, A. (1995). Management of giant tortoises Geochelone elephantopus and Geochelone gigantean at Zurich Zoological gardens. International Zoo Yearbook, 34(1), 135–143. doi:10.1111/j.1748-1090.1995.tb00671.x
[25] Global, S. D. Z. (2010). Galapagos tortoise fact sheet. Retrieved January 31, 2017, from http://library.sandiegozoo.org/factsheets/galapagos_tortoise/tortoise.htm
[26] Curtin, A. J., Zug, G. R., & Spotila, J. R. (2009). Longevity and growth strategies of the desert tortoise (Gopherus agassizii) in two American deserts. Journal of Arid Environments, 73(4-5), 463–471. doi:10.1016/j.jaridenv.2008.11.011
[27] Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research, 37(3), 614–636. doi:10.1016/0014-4827(65)90211-9
[28] Goldstein, S. (1974). Aging in vitro. Experimental Cell Research, 83(2), 297–302. doi:10.1016/0014-4827(74)90342-5
[29] Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25(3), 585–621. doi:10.1016/0014-4827(61)90192-6
[30] Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345(6274), 458–460. doi:10.1038/345458a0
[31] Girondot, M., & Garcia, J. (1999). Senescence and longevity in turtles: What telomeres tell us. 9th extraordinary meeting of the societas Europaea Herpetologica, 1, 25–29. Retrieved from //www.researchgate.net/publication/252290006_Senescence_and_longevity_in_turtles_What_telomeres_tell_us
[32] Miller, J. K. (2001). Escaping senescence: Demographic data from the three-toed box turtle (Terrapene carolina triunguis). Experimental Gerontology, 36(4-6), 829–832. doi:10.1016/s0531-5565(00)00243-6
[33] Schächter, F., Cohen, D., & Kirkwood, T. (1993). Prospects for the genetics of human longevity. Human Genetics, 91(6), . doi:10.1007/bf00205074
[34] Warner, D. A., Miller, D. A. W., Bronikowski, A. M., & Janzen, F. J. (2016). Decades of field data reveal that turtles senesce in the wild. Proceedings of the National Academy of Sciences, 113(23), 6502–6507. doi:10.1073/pnas.1600035113

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Hello to all.  I recently discovered this website/forums and look forward to participating.

 

Since I was in my teens, I was always interested in healthy living and eating and continue to be interested.  In recent years I have been trying supplements for various purposes.

 

 

User Agreement

by @ LongeCity - Articles

Bylaw A. User Agreement (Posting Guidelines)



Bylaw A. User Agreement

Article 1
The following shall be the letter of the agreement that all visitors, Members and their guests will be asked to abide by when interacting with the LongeCity/ Imminst ("LongeCity") website Please read this Agreement carefully before accessing the Site.

Section01 The Nature of this Agreement
(a) The following are the terms and conditions (the "Agreement") offered to any person ("you") for access and use (including but not limited to forum user registration) of the LongeCity/Immortality Institute (LongeCity) web site and all affiliated web sites (the "Site"). The Agreement is the basis for using and interacting with the LongeCity website. By accessing the Site, you agree to abide by this Agreement.
(b) Access to the Site is a privilege and not a right. If you do not agree with this Agreement, or have no intention to follow the rules outlined herein, you may not use the Site. If you have any reason to interact with a representative of LongeCity, but you do not wish to follow these rules, please email support@LongeCity.org
© The information in this document is subject to change. These changes will be announced on the Site, but you must also agree to periodically review this document for changes. After eight (8) days of any change in the Rules, your continued use of the Site indicates your acceptance of any changes made.

Section02 Account registration
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© You may not use the account of another person unless such use is inadvertent and infrequent (e.g. using a family members login from the same computer not noticing that the person forgot to log out).
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Section03 Content
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(b) Content from the Site may be downloaded solely for your own non-commercial use.
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(b) You acknowledge that the limitations set forth herein are integral to the amount of consideration levied in connection with the access and use of the Site and any services rendered hereunder and that, were LongeCity to assume any further liability other than as set forth herein, such consideration would of necessity be set substantially higher.
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(e) LongeCity does not verify the credentials of anyone contributing Content to the site and does not endorse any Content that is contributed as advice. Anyone providing advice and guidance on or in association with the site is doing this strictly in a personal capacity, whether or not this person has an official role with LongeCity, unless the advice is specifically, expressly and in each instance authorised by an LongeCity director. Users are reminded that 'Advisors' are advising the LongeCity board on policy. This does not constitute an endorsement by LongeCity of that Advisors communications with others.

Section06 Basic Prohibitions
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(i) Violate the Site's security including but not limited to accessing unauthorized data or logging into an account or attempt to log into an account for which you do not have authorization, scan or test for hardware or software
vulnerabilities, perform a denial of service attack, attempt to spread a virus or malware, or falsify TCP/IP information.
(j) Contributing any solicitation including but not limited to advertising, promotional materials, junk mail, spam, chain letters, pyramid schemes (also see section 8 below)

Section07 Content related to health
(a) Any and all advice and/or opinion provided is strictly personal and never endorsed by LongeCity, nor should it be construed to be the official policy of LongeCity to provide health advice.
(b) You must seek professional medical advice prior to embarking on any course or treatment associated with any Content on the Site.
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(d) All Information on the LongeCity Forums, including those associated with health, sciences fora are provided as an area for the open exchange of anecdotal experience and information, not as a professional source of advice.

Section08 Advertising, promotions and commercial activity
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(b) Advertising is any Content (including private messages) that draws attention to, solicits, endorses, offers for sale, links to, critiques or otherwise relates to goods or services where one of the parties involved in initiating such Content or one of their associates stands to benefit from financial transactions that may results from such Content.
(c) LongeCity seeks to limit surreptitious advertising where users who may have a financial stake in such matters contribute Content simply to increase product desirability or brand awareness. Such Content will be censored on the basis of suspicion alone. On occasion, 'innocent' Content may inadvertently be subjected to such censure. Users should be aware of this and are kindly asked to refrain from protest in these cases, as the common aim is to increase the quality of Content on the Site.
(d) Even if a promotion has been agreed by LongeCity, this does not imply, and no-one must imply that this constitutes an official endorsement by LongeCity of the promotion, the organisation and individual conducting the promotion or the promoted products or procedures.
(e) Users must not use the Site for initiating or conducting commercial transactions, whether in private messages, or by using contact details displayed on the Site unless expressly authorised by LongeCity.

Section09 Posting Guidelines
(a) Users must agree to consider the posting guidelines as specified in Article2. Adherence to these guidelines is monitored by LongeCity Moderators, Directors and other designated Officers.
(b) Violation of a guideline will incur a warning. Repeat violation on more than three separate occasions will result in a time-limited suspension of the user account ranging from eight days to eight years.
(c) Disputes regarding the enforcement of posting guidelines should be taken up, in the first instance, with the Moderator who has issued the warning. If no resolution can be found in dialogue, the dispute can be notified to the Lead Moderator. Warnings issued by the Lead Moderator can be disputed with the Secretary. Users who have an open dispute with a Moderator cannot be warned again by the same Moderator – but the Moderator in question may still report questionable posts by that user.
(d) LongeCity has reserved a forum for the expression of free speech known as the William O'Rights Memorial Forum. LongeCity will not restrict Content in this forum even if it violates the posting guidelines as long as such Content does not violate the other provisions in this Agreement. This is a forum where users can engage in 'flame wars', ensure that posts are not interfered with by a Moderator, or complain about LongeCity without threat of censure.


Article 2 Posting Guidelines

Section01 A-- General tone of conversations
A1-- Be polite. That does not mean that you cannot try to destroy another’s argument utterly but never lose your tone or your temper while doing so. Also under no circumstances should you employ personal judgments or remarks about people themselves rather than their arguments. Aside from the fact that such judgments are more often than not ill founded, they drag down the overall quality of the discussion as well as costing time and space.
A2-- Some words are generally considered offensive terms, in polite conversation such as "fuck, "shit", "faggot" or "nigger". Causing offence rarely if ever helps to elevate the quality of a discussion. Generally, use of such words will result in a warning or ban, but discretion may be exercised depending on the context.

Section02 B-- General writing style
B1-- Do not write excessive amounts of text. Be concise! No one has the time or the inclination to plough through a pile of superfluous rhetoric in order to discover your main points. If you really feel that you have to write an essay, then write a summary at the end as every considerate essay-writer would do.
B2-- While every caution is advised about over-using the forums design tools, please by all means DO use them, if this helps to make the text more accessible.

Section03 C-- Starting a new topic
C1-- Before starting a new topic please consider if the topic is informative, or will stimulate an interesting discourse.
C2-- Please check if the issue has been discussed before on the Site (It is not important to be a 100% sure about this – the LongeCity forums are quite large and old. But please make a quick search, especially if you have not been with the community for long. Sometimes, it may make sense to open a new topic anyway, but would be great if you could reference previous discussions.)
C3-- Please think about a good title. (This is very important. Please spend some time on considering the title. Titles like "A Question", "Hello" or "Life Extension" may lead to an otherwise interesting topic being deleted. Challenging titles may draw a lot of visitors will still incur a warning if they are not informative. Give full titles. "Vitamin E" is bad, "Vitamin E harmful?" is not as good as "Risk of Vitamin E supplements in Cancer".)
C4-- Is it a privileged topic? (LongeCity Members can create new topics over which they, as threadstarter have editorial control. This is to empower members who are willing to put in a bit of work to maximise the quality and values of a discussion thread. Other contributors must be alerted to the threadstarters intention in the first post, but cannot subsequently complain if their posts are edited.

Section04 D-- Replying to topics
D1-- Please ask yourself "Does my reply offer a significant contribution?"
D2-- It is critical that you try to keep follow-up posts on topic. Avoid going off on a different tangent. If it occurs to you that this might be another thread, open a new thread and put a link to it in the old one. The last word about relevance stays with the Moderators or the threadstarter.
D3-- As an extension of the previous point, do not derail a topic with fundamental critique even if you think that this would desirable. In particular do not question the necessity of a certain life-extension technique by referring to another method that seems more relevant to you. (Two examples: do not answer a question about the capacity of artificial intelligence to value human emotion correctly by stating that the ‘Singularity’ is a bunch of nonsense anyway; Do not intrude on an exchange about the bioavailability of resveratrol by stating that you don't care because you are signed up for cryonics)
D4-- Refrain from posting personal information unless it is inherently necessary to elaborate your views or position.
D5-- There is usually no benefit for people in reading that you agree unless you give an explanation to go with it.
D6-- You do not have to be an expert on the subject matter, but if you feel that you really don’t know enough about the subject, then ask informed questions before stepping into the ring for debate. If someone posts a link or uploads an article- read it before you go on. Also read the posts of your predecessors and be aware of related discussions elsewhere.

Section05 E-- Posting images
E1-- You are welcome to post your own images and drawings when they are relevant to sharing knowledge. Irrelevant or excessive positing of images, including emoticons (smiles) often diminishes quality of the Content and will likely incur a warning.
E2-- Showing images to illustrate a point or make a humorous quip is popular with some posters, but please consider if such posts could derail a discussion or create issues around copyright infringement.
E3-- Please be considerate about causing embarrassment when sharing images. As a rule of thumb, if you would be uncomfortable viewing it at work, do not post it.
E4-- Avatars: LongeCity encourages users to use a small portrait (passport-type) photograph as 'Avatar' of themselves, but this is not a requirement. However, the use of other peoples photographs or the LongeCity logo as Avatar is not allowed.

Section06 F-- Quotes and references
F1-- When replying to a previous post by quoting it, only quote precisely enough text as is necessary to understand your reply. Using the "reply" function in the forums will quote the entire post that you are replying to. Do not use this feature without due consideration.
F2-- If you quote, reference the quote properly, but only quote the important bits. (It is customary to put alterations to a quote in square brackets and indicate left-out bits by putting “...”) Do not quote whole articles, rather give a link or upload them. If you have to quote a substantial passage, then indicate the important passages that you want to draw attention too.
F3-- The use of references is strongly encouraged. Such references should contain enough information to find the relevant source with one or two mouse clicks. When using a link, please remember that the hypertext url may be specific to your own access and useless to others.

Fight Aging! Newsletter, February 12th 2018

by @ LongeCityNews

Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more.

This content is published under the Creative Commons Attribution 4.0 International License. You are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

To subscribe or unsubscribe please visit: https://www.fightaging.org/newsletter/

Contents

  • To Cure Aging as Though it Were a Disease
  • Decline in the Supporting Cells of the Blood-Brain Barrier Precedes Dementia
  • Models Suggest that Declining T Cell Production is the Primary Reason for Age-Related Increases in Cancer Risk
  • How Old is a Transplanted Organ?
  • A Few Recent Advances in Tissue Engineering and Regenerative Medicine
  • A New Blood Test Approach can Assess Levels of Amyloid-β in the Brain
  • Why is Life Span Inherited to any Significant Degree?
  • Immunosenescence and Inflammaging, Two Sides of the Same Coin
  • A More Subtle Demonstration that Telomere Length is Not a Good Measure of Aging
  • Reviewing What is Known of Extracellular Vesicles and Cellular Senescence
  • Ventricular Decline Correlates Well with Other Forms of Damage in the Aging Brain
  • Naked Mole-Rats Experience Cellular Senescence, but Seem Largely Unaffected by It
  • The Longest-Lived Bats Have Unusual Telomere Biology
  • MDM2 Antagonists Attenuate Harmful Signaling from Senescent Cells
  • Mitochondrially Targeted Antioxidant SS-31 Improves Cognitive Function in Old Mice

To Cure Aging as Though it Were a Disease
https://www.fightaging.org/archives/2018/02/to-cure-aging-as-though-it-were-a-disease/

Aging and cancer are conceptually similar in many ways, and by this I mean that they are both collections of processes that are fundamental to the way in which the biology of complex organisms works. They are not states that can be cured or eliminated through medicine as we presently understand it, but the aspiration is instead to bring these undesirable outcomes under control - to continually cut back the offshoots, to suppress the causes, and nip in the bud the results of those causes in their earliest stages. To actually cure either aging or cancer, to remove it from the human condition, would require a radical reworking of our cellular biochemistry, to the point at which it would cease to be biology in any meaningful sense and become a hybrid form of molecular nanotechnology. That sort of project lies far distant in the future. Today's concerns are entirely directed towards the control of aging and cancer, something that can be achieved through forms of medicine we can recognize and understand.

Regardless, we all use words carelessly. We search for cures for cancer. We call cancer a disease, though in reality this probably stretches that term as well. We choose not to call aging a disease, though not for any particularly rational reason. Having watched the progression of rejuvenation research since just after the turn of the century, it is both gratifying and interesting to see the changing tone in media coverage of the science, the message of the patient advocates, and the aspirations of those involved. Ten years ago, mockery was commonplace. Now journalists are taking it a lot more seriously; it is hard to do otherwise, given the earnest levels of funding and many scientific papers devoted to - to pick one example - the clearance of senescent cells, an actual, honest-to-goodness rejuvenation therapy now under development in various startup companies.

Nonetheless, journalistic habits of balance remain. Faced with a movement whose members want to prevent the majority of all death and suffering in the world by bringing an end to aging, and are mustering increasingly credible science to that cause, the authors of the old media still feel obliged to put in a word for the other side. After all, what about the view that everyone should just suffer and die? Why shouldn't that be presented with equal weight? After a certain point, balance becomes a caricature of itself - isn't this the sort of thing that would be put forth as satire in an earlier era? And yet here we are, death for everyone as the balance viewpoint in articles on the future rejuvenation biotechnology.

The Ambitious Quest to Cure Aging Like a Disease

The list of diseases humankind has managed to defeat is impressive. But throughout history, humans have suffered from a condition that they have never been able to escape - ageing. As we get older, our cells stop working as well and can break down, leading to conditions like cancer, heart disease, arthritis and Alzheimer's disease. Together, ageing-related diseases are responsible for 100,000 deaths per day and billions are spent around the world trying to slow their steady march on our bodies.

Some researchers, however, believe we may be thinking about these conditions in the wrong way. They say we should start treating ageing itself as a disease - one that can be prevented and treated. Their hopes are founded on recent discoveries that suggest biological ageing may be entirely preventable and treatable. From a biological perspective, the body ages at different rates according to genetic and environmental factors. Tiny errors build up in our DNA and our cells begin developing faults that can accumulate into tissue damage. The extent of these changes over time can mean the difference between a healthy old age or one spent housebound and afflicted by chronic diseases.

The scientists who hope to do this sit on the fringes of the mainstream medical landscape. But there are now a number of research centres around the world that have made identifying ways of preventing biological ageing a priority. Studies in animals have shown that it is indeed possible to dramatically extend the lifespan of certain species, giving hope that it could also be possible in humans. One of the leading figures in human longevity research, Aubrey de Grey, is the chief science officer at the Strategies for Engineered Negligible Senescence (SENS) Research Foundation, a California-based regenerative medicine research foundation focused on extending the healthy human lifespan. Their goal is to develop a suite of therapies for middle-aged and older people that will leave them physically and mentally equivalent to someone under the age of 30. They want "to fix the things we don't like about the changes that happen between the age of 30 and the age of 70". There are seven biological factors de Grey argues are predominantly responsible for cellular damage that accompanies ageing and underlies ageing-related diseases.

De Grey doesn't think that it will be possible stop ageing altogether with these types of approaches, but they may give patients an extra 30 years or so of life. He envisages a future where "rejuvenation technologies" can be administered to old people in order to revert their cells to what they were like when they were in their youth, buying them extra time. The idea is that someone who is treated at the age of 60 will be biologically reverted to 30. But because the therapies are not permanent fixes, their cells will end up becoming 60 years old again in another 30 years time. By then de Grey hopes the therapies could be reapplied as "version 2.0" to revert the same individuals once again to become younger in their cells. As a result, that person's cells wouldn't become 60 again until they're about 150 years old.

And he is not alone in believing ageing-related diseases can be solved. George Church, a geneticist at Harvard Medical School, told us that while some of his colleagues argue many age-related diseases are so complex that they simply can't be treated, he finds such thinking to be incorrect. "If you can control both the environment and the genetics, you can get people that live youthful healthy lives for exceptionally much longer than others. In industrialised nations, most of the diseases are due to age-related diseases and I think those too can be handled."

But regardless of how it is achieved, extending human lifespans by decades or even hundreds of years will present us with some difficult social realities. There could be major societal impacts if we all start living longer. There are some that fear greater longevity could lead to swelling populations and raise doubts that our planet could support such numbers. Aubrey de Grey has little time for such questions and believes that other technologies - such as artificial meat, desalination, solar energy and other renewables - will increase the carrying capacity of the planet, allowing more people to live longer lives. But this rationale suffers from a dependence on uncertain techno-fixes that may not alleviate suffering in an equally distributed manner. Yet, if concerns like these had paralysed the early pioneers of vaccination and antibiotics, it is unlikely many of us today could expect to live much beyond the age of 40-years-old. Advances in medicine over the last two centuries have taught us that we have the power to defeat the diseases that afflict us. Perhaps if we apply ourselves, then we can beat ageing too.

Decline in the Supporting Cells of the Blood-Brain Barrier Precedes Dementia
https://www.fightaging.org/archives/2018/02/decline-in-the-supporting-cells-of-the-blood-brain-barrier-precedes-dementia/

The brain is locked away from the biochemistry of the rest of the body behind the blood-brain barrier, the sheath of specialized cells surrounding blood vessels in the brain that prevents most unwanted molecular traffic to and from neural tissues. The brain is biochemically quite different from the rest of the body, and many of the commonplace molecules found elsewhere can be harmful to brain tissue or degrade neural function. Pericytes are one of the supporting cell types involved in the structure of the blood-brain barrier, and in the research noted here, pericyte dysfunction is linked to other known aspects of biochemical disarray in the vascular system that take place with aging. These include: the leakage of fibrinogen into the brain and its damaging effects on nerves; the progressive failure of blood-brain barrier integrity, allowing other forms of leakage; the buildup of protein aggregates that harm neurons; and the general vascular dysfunction that impacts the delivery of nutrients to the energy-hungry brain.

What can be done about this? The research here identifies the functional failure of pericytes as the earliest cause in the stack of consequences that the authors examined, but they look at managing fibrinogen as the first option for therapies. This is a sadly common sort of approach, meaning to work on the manipulation of consequences rather than addressing lower causes. To my eyes, the better way forward would be to dig deeper into the dysfunction of the cells of the blood-brain barrier, to ask why they are declining. There is a rich literature of investigation regarding blood vessel dysfunction, one that is starting to touch on the contributions of the root causes of aging, such as cellular senescence. More could certainly be done in that direction, rather than immediately preparing the ground for attempts at clinical translation of what has been learned so far.

Half of all dementias, including Alzheimer's, start with damaged 'gatekeeper cells'

Nearly 50 percent of all dementias, including Alzheimer's, begins with the breakdown of the smallest blood vessels in the brain and their protective "gatekeeper cells," according to a new study. That catastrophe causes a communications failure called small vessel disease. Many people with that disease also have white matter disease, the wearing away of fatty myelin that allows neurons to transfer messages within the brain network. In an animal model, researchers found that brain deterioration associated with dementia may start as early 40 in humans.

For more than 25 years, scientists have known that white matter disease impedes a person's ability to learn or remember new things, slows thinking and causes people to fall more often due to balance issues. They identified a link between crippled small blood vessels in the brain and white matter disease but didn't know what started that process until now. "Many scientists have focused their Alzheimer's disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier - with leaky blood vessels in the brain. The collapse of pericytes - gatekeeper cells that surround the brain's smallest blood vessels - reduces myelin and white matter structure in the brain. Vascular dysfunctions, including blood flow reduction and blood-brain barrier breakdown, kick off white matter disease."

The study explains that pericytes play a critical role in white matter health and disease via fibrinogen, a protein that circulates in blood. Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produce myelin), to die. The researchers are the first to show that fibrinogen is a key player in non-immune white matter degeneration. The protein enters the brain through a leaky blood-brain barrier. The study found about 50 percent fewer gatekeeper cells and three times more fibrinogen proteins in watershed white matter areas in postmortem Alzheimer's brains of humans compared to healthy brains.

To confirm that fibrinogen proteins are toxic to the brain, researchers used an enzyme known to reduce fibrinogen in the blood and brain of mice. White matter volume in mice returned to 90 percent of their normal state, and white matter connections were back to 80 percent productivity. "Our study provides proof that targeting fibrinogen and limiting these protein deposits in the brain can reverse or slow white matter disease. It provides a target for treatment, but more research is needed. We must figure out the right approach. Perhaps focusing on strengthening the blood-brain barrier integrity may be an answer because you can't eliminate fibrinogen from blood in humans. This protein is necessary in the blood. It just happens to be toxic to the brain."

Pericyte degeneration causes white matter dysfunction in the mouse central nervous system

Diffuse white-matter disease associated with small-vessel disease and dementia is prevalent in the elderly. The biological mechanisms, however, remain elusive. Using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, and behavior and tissue analysis, we found that pericyte degeneration disrupted white-matter microcirculation, resulting in an accumulation of toxic blood-derived fibrin(ogen) deposits and blood-flow reductions, which triggered a loss of myelin, axons, and oligodendrocytes. This disrupted brain circuits, leading to white-matter functional deficits before neuronal loss occurs.

Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition, pericyte degeneration, vascular pathology and white-matter changes. Thus, our data indicate that pericytes control white-matter structure and function, which has implications for the pathogenesis and treatment of human white-matter disease associated with small-vessel disease.

Models Suggest that Declining T Cell Production is the Primary Reason for Age-Related Increases in Cancer Risk
https://www.fightaging.org/archives/2018/02/models-suggest-that-declining-t-cell-production-is-the-primary-reason-for-age-related-increases-in-cancer-risk/

In the open access paper noted here, researchers use modeling to suggest that age-related decline of the thymus, and thus of the immune system, is more important than mutation as a determinant of cancer risk. Cancer is at root caused by mutational damage to DNA. While DNA repair and replication mechanisms are highly efficient, mutations nonetheless occur - and must occur at some rate in order for evolution to take place. It is a numbers game, in that the more time, the more cells, and the more cell activity, the greater the odds that a cancerous mutation will occur. Mutation rates are also affected by external factors such as radiation, toxic molecules in the cellular environment, and other forms of stress put upon cells. But this is just the primary cause, the trigger enables a cell to replicate without restraint.

After a mutation occurs, there are several classes of process that work to shut down or destroy potentially cancerous cells. We suffer countless potential cancers in our lives, but near all are suppressed before they start. The first line of defense is internal to cells: mechanisms such as those related to p53 that can respond to cancerous mutations and aberrant behavior by inducing immediate programmed cell death or inducing the state of cellular senescence. The latter shuts down replication, sets the cell on the path to self-destruction via apoptosis, and further issues signaling that calls in the immune system to destroy the errant cell. The immune system is the second, and perhaps more important line of defense. Immune cells of various types aggressively seek out and destroy cells that show signs of cancer or other undesirable behavior.

Unfortunately, the immune system declines in effectiveness with age. One of the reasons for this decline is a slowing of the rate at which new T cells are created. This is in part a question of the loss of stem cell activity that occurs throughout the body, reducing the generation of new cells of all sorts. Perhaps more important in the case of T cells is the age-related atrophy of the thymus, however. This organ is where T cells mature before taking up their assigned roles in the body. It is highly active in childhood, but the active tissue begins to be replaced by fat at the onset of maturity, a process called involution. This continues over a life span and into old age, and the pace at which new T cells mature falls along with it.

A slow rate of T cell replacement causes the existing specialized and active T cell populations to become ever more worn and ragged, lacking reinforcements that can respond effectively to new challenges. This affects most of the aspects of immune function, from the response to invading pathogens to the ability to catch and destroy cancerous cells before they start in earnest the process of generating a tumor. For this reason there is considerable interest in the research community in finding ways to rejuvenate the thymus, to restore the active tissue that acts as a nursery for T cell maturation. If successful, this should go some way towards regaining the lost capacity of the immune system.

Thymic involution and rising disease incidence with age

T cells develop from hematopoietic stem cells as part of the lymphoid lineage and have the ability to detect foreign antigens and neoantigens arising from cancer cells. In the thymus, lymphoid progenitors commit to a specific T cell receptor and undergo selection events that screen against self-reactivity. Cells that pass these selection gates then leave the thymus, clonally expanding to form the patrolling naive T cell pool.

The vast majority of vertebrates experience thymic involution (or atrophy) in which thymic epithelial tissue is replaced with adipose tissue, resulting in decreasing T cell export from the thymus. In humans, this is thought to begin as early as 1 year of age. The rate of thymic T cell production is estimated to decline exponentially over time with a half-life of ∼15.7 years. Declining production of new naive T cells is thought to be a significant component of immunosenescence, the age-related decline in immune system function. With the recent successes of T cell-based immunotherapies, it is timely to assess how thymic involution may affect cancer and infectious disease incidence.

It is clear from epidemiological data that incidence of infectious disease and cancer increases dramatically with age, and, specifically, that many cancer incidence curves follow an apparent power law. The simplest model to account for this assumes that cancer initiation is the result of a gradual accumulation of rare "driver" mutations in one single cell. Furthermore, the fitting of this power law model (PLM) can be used to estimate the number of such mutations. Exponential curves have also been used to fit cancer incidence data, resulting in worse fits than the PLM overall. Nevertheless, it is worth noting that exponential rates close to the declining curve for thymic T cell production can be seen to emerge from the incidence data, indicating the relevance of the thymic involution timescale. While the PLM fits well, it does not account for changes in the immune system with age. To better determine the processes underlying carcinogenesis, we asked whether an alternative model, based only on age-related changes in immune system function, might partly or entirely explain cancer incidence.

Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. Our hypothesis and results add to the understanding of infectious disease and cancer incidence, suggesting in the latter case that immunosenescence, rather than gradual accumulation of mutations, serves as the predominant reason for an increase in cancer incidence with age for many cancers. For future therapies, including preventative therapies, strengthening the functionality of the aging immune system appears to be more feasible than limiting genetic mutations, which raises hope for effective new treatments.

How Old is a Transplanted Organ?
https://www.fightaging.org/archives/2018/02/how-old-is-a-transplanted-organ/

Heterochronic parabiosis involves joining the circulatory system of two animals, one old, one young, in order to observe the results. At a high level, the older individual exhibits reversal of some aspects of aging, and the young individual exhibits acceleration of some aspects of aging. The details are complex, and still debated in many cases, however. Researchers see this phenomenon as one of the more effective paths forward to identifying the important age-related changes in the environment of signals generated by cells that find their way into the bloodstream. A more effective approach would be to repair the underlying damage that causes aging - and thus also causes signaling changes - but the technologies to achieve that goal barely exist yet. Of the needed approaches, only clearance of senescent cells via senolytic pharmaceuticals is both easily studied in the laboratory and producing a great deal of useful data.

Branching out from the initial focus on joined circulatory systems, there are numerous other possible approaches to mixing young and old signals and tissues. Groups are assessing the results of transfusions of blood or plasma from young to old, for example, with Alkahest and Ambrosia as two of the more public examples. There is mixed data for the effectiveness of this strategy in comparison to parabiosis, however. The nature of the interactions when blood is circulating through two bodies is significantly different from that of even regular transfusions, and that may be important. For example, what if outcomes depend upon young tissues reacting to signals present in old blood and stepping up beneficial activities in response?

Looking further afield, we might consider investigating the transplantation of organs and other large tissue sections. The organ donation and transplant industry is, in effect, an enormous natural experiment in what happens when tissues are placed into an older or younger environment. It further has the advantage of providing human data rather than animal data. What would we expect to happen when an old organ is placed into a younger body? We might expect a degree of functional rejuvenation, and that can be measured, and the details of the biochemistry assessed. Equally, we may expect that some of the damage of aging and consequent impairment of organ function will not be reverted. Human biochemistry doesn't appear to be capable of effectively clearing persistent cross-links that stiffen tissues, for example.

The logistics of obtaining data from this experiment are not quite straightforward, however. While tens of thousands of organ transplants take place every year, and there are at least hundreds of thousands of recipients still alive, tracking down past patients and connecting them reliably with medical records is an expensive proposition. Also, the more recent data is the more interesting data. The viable approach is thus to work with medical establishments for ongoing transplant procedures and the necessary followups. In this way a fair-sized study set and database could be accumulated in a year or two. The authors of this paper have made a start on such an effort, and it is interesting to see that the narrow slice of data they elected to survey shows little rejuvenating effect when old livers are transplanted into young recipients. There is, however, a negative impact when young livers are transplanted into old recipients.

Biological age of transplanted livers

The scarcity of human donor organs in terms of availability for transplants is a renowned problem. The high request of organs moves toward an increased use of marginal donors, including organs from old or very old donors usually transplanted into younger recipients. Within the context of orthotopic liver transplants, clinical evidence suggests that livers from aged donors (≥ 70 years) do have function and duration comparable to those achievable with livers from younger donors. Paradigmatic are the cases of 26 octogenarians livers being transplanted between 1998 and 2006, 15 patients out of 26 are currently alive and 2 of those organs being centenarians.

Our team was deeply involved in an Italian national project to collect biological data to answer the question - why livers from old donors may be successfully used for transplants. The first evidence was a relative low grade of aging signs of liver donors at histological and cytological level, also including the three major proteolytic activities of proteasome, comparing young and old livers. Further, we tried to investigate the epigenetic age-related modifications in terms of liver microRNAs (miRs). We discovered that at 60-70 years of chronological age, three miRs start to increase their expression level, i.e. miR-31-5p; miR-141-3p; miR-200c-3p, and we assumed such an increase as markers of aging in human liver. When a relatively young liver was transplanted into a relatively older recipient (Δ age-mismatch average: +27 years) the expression of these miRs significantly increased in the organ (follow up after graft at 15 ± 7 months). It is interesting that we were not able to document the reverse. Indeed, when a relatively old liver was transplanted into a relatively young recipient (Δ age-mismatch average: -17 years), the expression of the three above-mentioned miRs did not change (follow up after graft at 10 ± 2 months).

On the whole, these observations suggest that in the setting of liver transplantation the aging phenotype can be "transmitted/propagated" more easily than the young phenotype via the body microenvironment. Recently, we studied the above mentioned miRs using single-miR real time-RT qPCR on blood serum samples from 34 recipients stratified on the basis of donor liver chronological age. No difference was observed, thus suggesting that the phenomenon previously found was tightly related to the organ itself without miR-specific exocytosis and changes at circulating level, at least for the identified miRs.

The biological effect of donor and recipient age-mismatch is a topic rather neglected despite its great potential, biological and clinical interest. The possibility that a centenarian liver can still function properly may suggest not only the intrinsic peculiarity of this organ (slowed down ageing; regeneration phenomena), but also the interaction with the younger recipients. This interaction was previously demonstrated in heterochronic parabiosis experiments in mice models, but deep analyses need specifically in humans, aiming at explain the reason of the variability associated with the duration of transplant.

A Few Recent Advances in Tissue Engineering and Regenerative Medicine
https://www.fightaging.org/archives/2018/02/a-few-recent-advances-in-tissue-engineering-and-regenerative-medicine/

The tissue engineering and regenerative medicine communities are too large and energetic to do more than sample their output, or note the most interesting advances that stand out from the pack. The publicity materials I'll point out here are a recent selection of items that caught my eye as they went past. Dozens more, each of which would have merited worldwide attention ten or fifteen years ago, drift by with little comment every year. The state of the art is progressing rapidly towards both the ability to build complex tissues from a cell sample, such as patient-matched organs for transplantation, and the ability to control regeneration and growth inside the body. Ultimately we may not need transplantation if native organs can be persuaded to repair themselves ... but this will likely also require significant progress towards repairing the cell and tissue damage of aging, the forms of molecular breakage that degrade regenerative capacity.

Even though the research community has progressed a long way past the capabilities of even a decade ago, there remains a longer road ahead. Transplants of cell populations are still very challenging; only a small fraction of those cells survive to take up residence and contribute over the long term. The best technology demonstrations manage 10% survival or thereabouts. Standard approaches to finding the best methodology for each cell type and situation have yet to arise. There is a lot of trial and error. Yet replacement of cell populations, reliably, and with high quality, youthful, undamaged cells, is needed to treat many of the consequences of aging. Consider the loss of dopamine-generating neurons in Parkinson's disease, for example, or the wearing down of the stem cell population responsible for generating the immune system, or the structural remodeling and weakening of the heart in response to hypertension. Removing the damage that caused those issues will not automatically restore all of the losses.

Researchers report first lung stem cell transplantation clinical trial

For the first time, researchers have regenerated patients' damaged lungs using autologous lung stem cell transplantation in a pilot clinical trial. In 2015, the researchers identified p63+/Krt5+ adult stem cells in a mouse lung, which had potential to regenerate pulmonary structures including bronchioles and alveoli. Now they are focusing on lung stem cells in humans rather than mice. The researchers found that a population of basal cells labeled with an SOX9+ marker had the potential to serve as lung stem cells in humans. They used lung bronchoscopy to brush off and amplify these lung stem cells from tiny samples.

In order to test the capacity of lung stem cells to regenerate lung tissue in vivo, the team transplanted the human lung stem cells into damaged lungs of immunodeficient mice. Histological analysis showed that stem cell transplantation successfully regenerated human bronchial and alveolar structures in the lungs of mice. Also, the fibrotic area in the injured lungs of the mice was replaced by new human alveoli after receiving stem cell transplantation. Arterial blood gas analysis showed that the lung function of the mice was significantly recovered.

The team launched the first clinical trial based on autologous lung stem cell transplantation for the treatment of bronchiectasis. The first two patients were recruited in March 2016. Their own lung stem cells were delivered into the patients' lung through bronchoscopy. One year after transplantation, two patients described relief of multiple respiratory symptoms such as coughing and dyspnea. CT imaging showed regional recovery of the dilated structure. Patient lung function began to recover three months after transplantation, which maintained for one year.

Scientists create functioning kidney tissue

Kidney glomeruli - constituent microscopic parts of the organ - were generated from human embryonic stem cells grown in plastic laboratory culture dishes containing a nutrient broth known as culture medium, containing molecules to promote kidney development. They were combined with a gel like substance, which acted as natural connective tissue - and then injected as a tiny clump under the skin of mice. After three months, an examination of the tissue revealed that nephrons: the microscopic structural and functional units of the kidney - had formed.

Tiny human blood vessels - known as capillaries - had developed inside the mice which nourished the new kidney structures. However, the mini-kidneys lack a large artery, and without that the organ's function will only be a fraction of normal. So, the researchers are working with surgeons to put in an artery that will bring more blood the new kidney. "We have proved beyond any doubt these structures function as kidney cells by filtering blood and producing urine - though we can't yet say what percentage of function exists. What is particularly exciting is that the structures are made of human cells which developed an excellent capillary blood supply, becoming linked to the vasculature of the mouse. Though this structure was formed from several hundred glomeruli, and humans have about a million in their kidneys - this is clearly a major advance. It constitutes a proof of principle - but much work is yet to be done."

New tissue-engineered blood vessel replacements closer to human trials

Researchers have created a new lab-grown blood vessel replacement that is composed completely of biological materials, but surprisingly doesn't contain any living cells at implantation. The vessel, that could be used as an "off the shelf" graft for kidney dialysis patients, performed well in a recent study with nonhuman primates. It is the first-of-its-kind nonsynthetic, decellularized graft that becomes repopulated with cells by the recipient's own cells when implanted.

The researchers generated vessel-like tubes in the lab from post-natal human skin cells that were embedded in a gel-like material made of cow fibrin, a protein involved in blood clotting. Researchers put the cell-populated gel in a bioreactor and grew the tube for seven weeks and then washed away the cells over the final week. What remained was the collagen and other proteins secreted by the cells, making an all-natural, but non-living tube for implantation.

To test the vessels, the researchers implanted the 15-centimeter-long (about 5 inches) lab-grown grafts into adult baboons. Six months after implantation, the grafts grossly appeared like a blood vessel and the researchers observed healthy cells from the recipients taking up residence within the walls of the tubes. None of the grafts calcified and only one ruptured, which was attributed to inadvertent mechanical damage with handling. The grafts after six months were shown to withstand almost 30 times the average human blood pressure without bursting. The implants showed no immune response and resisted infection.

A New Blood Test Approach can Assess Levels of Amyloid-β in the Brain
https://www.fightaging.org/archives/2018/02/a-new-blood-test-approach-can-assess-levels-of-amyloid-%ce%b2-in-the-brain/

Researchers have developed a blood test that correlates well with levels of amyloid-β in the brain, offering an opportunity to reduce the cost of assessing potential therapies to treat Alzheimer's disease. Currently the only reliable methods are invasive or expensive, requiring access to cerebrospinal fluid or the use of scanning technologies. This work might be considered in the broader context of a range of studies linking amyloid-β in blood vessels and bloodstream with amyloid-β in the brain; it is thought that the relationship between amyloid-β inside and outside the brain may be a two-way street, a form of equilibrium. On the one hand that means that it might be possible to leach amyloid-β from the brain by clearing it from the cardiovascular system. On the other hand, it may be the case that increased amyloid-β in the cardiovascular system due to aging is an early source of the amyloid protein aggregates that emerge in the brain.

Researchers have developed the first blood test to detect amyloid-β protein buildup in the brain, one of the earliest hallmarks of Alzheimer's disease. The findings show that measurements of the protein and its precursors in the blood can predict neural amyloid-β deposition and could pave the way for a cheap and minimally invasive screening tool for the disease. "This study has major implications. It is the first time a group has shown a strong association of blood plasma amyloid with brain and cerebrospinal fluid."

Current methods to identify amyloid-β buildup in living people are limited to costly and sometimes highly invasive procedures, such as brain imaging with a PET scanner and spinal cord fluid extraction. So researchers set out to test whether the same information could be obtained from a blood sample. Using immunoprecipitation and mass spectrometry, the team isolated and characterized amyloid proteins in the blood from a cohort of 121 people in Japan spanning a range of cognitive function, from normal to developed Alzheimer's. They showed that blood test results could predict amyloid-β levels in the brain with about 90 percent of the accuracy achieved using PET scanning. A repeat of the approach with a validation cohort of 252 people in Australia confirmed the blood test's performance.

Such a test could one day be used to detect early signs of Alzheimer's in people with no obvious symptoms. "I can see in the future, five years from now, where people have a regular checkup every five years after age 55 or 60 to determine whether they are on the Alzheimer's pathway or not. If a person knows they are on this pathway well before the onset of any cognitive impairment some would want to alter their lifestyles. It's good to see this type of study advance, as we desperately need noninvasive and low-cost markers for Alzheimer's disease. But still, at this point it is not ready for prime time."

Why is Life Span Inherited to any Significant Degree?
https://www.fightaging.org/archives/2018/02/why-is-life-span-inherited-to-any-significant-degree/

Why do the life spans of parents exhibit some degree of correlation with the life spans of their children? "Genetics" is probably not an acceptable answer, given present evidence for natural genetic variation to contribute comparatively little to human life expectancy in all but a few rare cases. So is it cultural, where culture influences lifestyle choices closely correlated with health, such as weight gain or smoking? Or is it due to wealth effects, for much the same reasons? If so, then why is there such variation in life expectancy within specific social groups and wealth strata? These are tough questions to answer with any reliability given snapshot data from groups within human populations. Any given large study is just a single data point in the ongoing process of analysis and debate that spans decades and the entire scientific community.

In the long run, I have my doubts that good answers will be established for this and many other questions regarding the details of natural aging today. We may never know. The urge to investigate the demographics of aging will be swept away by the advent of rejuvenation therapies such as the senolytics presently under development. All natural variations in pace of aging and life expectancy will be buried beneath the size of the gains made possible through periodic repair of the cell and tissue damage that causes aging. The data will evaporate, and different concerns will occupy the scientific community of tomorrow. After all, how many members of today's scientific community spend any time on the demographics of smallpox in populations lacking treatment options? Few indeed. It will be the same for natural aging.

Mortality, life expectancy, and age-at-death are all strongly socially structured. Despite economic growth, welfare state provisions, modern medicine and a fundamental change in disease panorama, we find a negative social gradient in mortality generation after generation. Because education, occupation, and income all predict health and survival we should also expect such characteristics in the parental generation to predict the next generation's health prospects, resulting in "inheritance of longevity". It is possible, however, that this influence from previous generations is considerably broader than that working through the children's own education, occupation, and income. Variation in mortality risk within social groups is great. To understand "inheritance of longevity" we need a conceptual framework that also identifies those within-class influences.

Already in 1934 it was suggested that the first 15 years of life could determine your mortality risk during the entire lifecourse. Similarly, the so-called DOHaD (Developmental Origins of Health and Disease) theory suggests that early life experiences is an important determinant of adult health and disease. DOHaD theory has focused on specific aetiologies and influences, such as that of foetal growth restriction on blood pressure and circulatory disease. Another, earlier school of thinking argued for more general disease-causing mechanisms. Concepts like frailty, general susceptibility, or differential vulnerability refer to individual differences in the ability to survive hardship.

Demographic concepts like frailty, epidemiological ones like general susceptibility, and psychological ones like resilience all refer to the same real-life-phenomenon: a general rather than specific vulnerability to disease. Some have stressed its social roots, while others perhaps assumed it to have a more genetic basis. Resilience, in turn, may be related to both views. It could be thought of as the opposite extreme to susceptibility/frailty on the same underlying dimension. In this study, we argue that resilience is acquired early and maintained throughout life. Resilience should therefore influence the ability to survive up to a high age and be linked to longevity, as a number of studies indeed suggest.

"Inheritance of longevity" has been discussed at length in the literature. Its precise nature is somewhat elusive. Studying the entire Icelandic population, researchers concluded that longevity was inherited within families, probably because of shared genes. Other groups, looking at twin data, concluded that genetic influences on the lifespan were minimal before age 60 and only increase after that age. On the other hand, other work has rejected any idea that mortality in old age is genetically programmed. Consistent with that view, a Swedish study of men born in 1913, found that a number of social and behavioural factors measured at age 50, but not their parents' survival, predicted longevity.

Evolutionary theorists have debated whether there is any evolutionary pressure to promote survival into old age. Nevertheless, we observe a steady lifespan extension in modern societies, especially among women, partly based on falling mortality rates across their long post-reproductive period. That children tend to live longer than their parents is likely to be determined both by what experience parents brings to the next generation, and by the improved life circumstances of the children themselves in their childhood and adult life. The importance of genetic factors for longevity, we suggest, may lie in their interaction with other factors, perhaps especially if this interaction takes place at an early age.

Immunosenescence and Inflammaging, Two Sides of the Same Coin
https://www.fightaging.org/archives/2018/02/immunosenescence-and-inflammaging-two-sides-of-the-same-coin/

The aging immune system falls apart in a number of different ways, and as the researchers here note, the process probably isn't just one of decline, but of a continual adaptation to that decline. Present nomenclature tends to categorize aspects of immune system aging into broad categories by the type of outcome produced. These are (a) immunosenescence, the weakening of the immune response to pathogens and failure of immune surveillance of potentially dangerous cells, (b) inflammaging, progressively raised levels of chronic inflammation, and © autoimmunity, in which the immune system begins to attack tissues. In reality, everything in biochemistry is connected to everything else, and these outcomes are the consequences of interacting, shared processes of decline and damage.

Any successful effort to turn back immune system aging, such as by selectively destroying malfunctioning or unhelpfully configured immune cells, and restoring the generation of new immune cells to youthful levels, should go some way to addressing all of these issues. The researchers here suggest caution on selective reversal of symptoms of immune aging, as some are beneficial adaptations, but in my opinion this shouldn't apply to efforts to address the lower level causes of immune aging. Where adaptations occur, they are adaptations to those causes, an attempt to claw back some functionality in the face of decline. That becomes moot, and the adaptation should cease, if its trigger is removed.

Aging is one of the most intricate and complex biological phenomenon. One physiological system that shows marked changes during aging is the immune system. The interest of the immune system in aging is related to the fact that this is an interacting master regulatory system that keeps the organism free of invaders, either internal or external. Since the introduction of the notion of immunosenescence, many scientists have questioned the justification for unidirectional implication of the immune system and its decreased efficiency associated with aging. Whereas some functions are indeed decreased, others are increased. Therefore; changes are not as uniform as the designation would suggest.

Accordingly, we can propose a new paradigm for dynamic immune changes with aging. We suggest that aging leads to modified/modulated responses of the immune system, making it more adapted to cope with challenges (pathogens) in a given (local) environment, and not just to an eventually terminal deterioration of the immune system. From an evolutionary perspective, this is a simple optimization of the resources of the aging body, even if it ultimately leads to pathologies and death. Immunosenescence may be necessary for an adequate response to known antigens, but detrimental for responses to new antigens in most circumstances. From this perspective, many or most age-related changes in the immune system may be desirable adaptations to the aging process, and thus no need for rejuvenation seems to be necessary.

In conclusion, most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflammaging. Together, immunosenescence and inflammaging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system.

If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflammaging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened.

A More Subtle Demonstration that Telomere Length is Not a Good Measure of Aging
https://www.fightaging.org/archives/2018/02/a-more-subtle-demonstration-that-telomere-length-is-not-a-good-measure-of-aging/

Researchers here find a disconnect between DNA methylation patterns shown to correlate well with age and processes associated with longer telomere length. Telomeres are caps of repeated DNA at the ends of chromosomes that shorten with each cell division, a part of the mechanism limiting the life span of somatic cells. Their average length tends to shorten with age when considered across large populations in a statistical analysis, but this is a tenuous relationship that has also failed to appear in some smaller studies. Here, it seems that older ages as assessed by DNA methylation can correlate with differences in telomerase, the enzyme responsible for lengthening telomeres, that are associated with longer telomeres.

In any given individual, average telomere length as currently measured in leukocytes from a blood sample is dynamic in response to circumstances; it reflects pace of cell division and the rate at which new cells with long telomeres are generated by stem cells. Unfortunately the large degree of individual and circumstantial variation means that there is little to be meaningfully said about the present value - the information is not actionable in all but rare cases of exceptionally short average length due to disease. The epigenetic clocks derived from DNA methylation measurements are much more solid, repeatable, useful metrics, judging from the evidence to date.

In that broader context, it is interesting to find signs that these two approaches to measuring an aspect of aging are not on the same page, though I think the researchers here overstate the significance of their work and/or engage with a strawman to some degree in their comments. What they have found does fit in with the evidence to date supporting the idea that telomere length is only very loosely associated with aging, with considerable variation between individuals. That is somewhat distinct from the question of whether or not telomerase gene therapies are a useful approach to the treatment of aging or other conditions.

Researchers analyzed blood samples from nearly 10,000 people to find that genetic markers in the gene responsible for keeping telomeres (tips of chromosomes) youthfully longer, did not translate into a younger biologic age as measured by changes in proteins coating the DNA. DNA methylation age is a biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown.

In this genome-wide association study, researchers found gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration. Variants in the gene called Telomerase Reverse Transcriptase (TERT) on chromosome 5 that were associated with older IEAA were also associated with longer telomeres indicating a critical role for TERT in regulating the epigenetic clock, in addition to its established role of compensating for cell replication-dependent telomere shortening.

"We calculated the epigenetic aging rate for each person using a previously described epigenetic clock method. Next, we related the epigenetic aging rate to millions of genetic locations (SNPs) across all of the chromosomes. Then we studied the SNPs that had very significant associations with epigenetic aging rates. To our surprise, one of these locations was the TERT locus. The finding is surprising because this was not a study of telomere length. TERT is a subunit of the enzyme telomerase, which is widely known because it has been touted as an anti-aging enzyme. Our study highlights the error in the notion that activation of telomerase (as advocated by some) will cure aging. Instead, our study shows that an anti-aging therapy based on telomerase expression would be accompanied by continued aging."

Reviewing What is Known of Extracellular Vesicles and Cellular Senescence
https://www.fightaging.org/archives/2018/02/reviewing-what-is-known-of-extracellular-vesicles-and-cellular-senescence/

The research community has been devoting more time and energy to the investigation of extracellular vesicles of late. These membrane-bound packages of proteins and other molecules are an important facet of the way in which cells communicate with one another. Signaling between cells is itself very significant, a potential point of intervention for many classes of therapy. For example, most current stem cell therapies appear to work largely due to the signaling provided by transplanted cells - given sufficient understanding of the signaling, the cells could be dispensed with and the signals applied directly.

As another example, the growing presence of cellular senescence with age has a large detrimental impact on tissue function, despite the comparatively small numbers of senescent cells present even in older individuals, because these negative effects are mediated by signaling. In this way, a handful of errant cells can put the entire local environment into disarray. On that topic, the open access paper here takes a short tour of what is known about extracellular vesicles in the context of cellular senescence.

Cellular senescence prevents the proliferation of cells exposed to potentially oncogenic stresses, such as DNA-damaging reagents, irradiation, telomere shortening, and oncogene activation. Mutations in genes essential for the senescence-induced cell cycle arrest predispose cells to immortalization and shorten lifespan by increasing cancer incidence. However, cellular senescence not only arrests the cell cycle but also changes how the cell impacts its microenvironment. The way in which senescent cells influence their microenvironment is highly context dependent. It promotes tumor development in many cases, but can also be tumor suppressive in certain circumstances. Removal of senescent cells that accumulated in the body during aging alleviates atherosclerosis, hepatic steatosis, tumor development, and functional declines of heart, kidney, and fat tissues, resulting in prolonged healthspan and lifespan. These effects may be attributable to so-called , whereby cells secrete high levels of inflammatory cytokines, chemokines, growth factors, and metalloproteinases.

Although the involvement of typical secretory proteins in the non-cell-autonomous effects of senescent cells has been well studied, the functions of membrane-enclosed vesicles secreted by senescent cells have not been studied until recently. These extracellular vesicles (EVs) were once thought to be cellular trash, but now it is clear that they are critical mediators in intercellular communication. Emerging evidence indicates that EVs also play important roles in cellular senescence and aging. This field is rapidly advancing especially since it was reported that EVs deliver functional RNA to the recipient cells. Extracellular vesicles contain a huge variety of proteins and nucleic acids in a cell type-dependent manner.

Senescence-associated increase in EV secretion seems to be a general feature of cellular senescence and has been observed in fibroblasts, epithelial cells, and cancer cells. This increase is at least partially mediated by p53 and one of its targets, TSAP6, although the mechanism whereby TSAP6 regulates EV secretion is not well understood. It is known that EV secretion contributes to the clearance of harmful molecules in cells, such as cytoplasmic DNA. It has been shown that EV-mediated removal of cytoplasmic DNA is essential for the survival of senescent cells, which may explain why EV secretion is increased in senescent cells.

Recent findings implicate senescent cell EVs in cancer development, vascular calcification, and age-related decline in bone formation. Increased secretion of EV-associated DNA from senescent cells is likely to be pro-inflammatory and may contribute to age-related chronic inflammation. Whether senescent cell EVs promote or suppress cancer development may be context dependent. Despite this progress, it should be noted that the functions of senescent cell EVs are still understudied, at least partially due to inadequate understanding of EVs themselves. This research field is immature and the methods used are not sufficiently standardized yet. Nevertheless, EVs are now shown to be critical players in cellular senescence and aging, and more functions will be revealed in the future as the EV research field matures.

Ventricular Decline Correlates Well with Other Forms of Damage in the Aging Brain
https://www.fightaging.org/archives/2018/02/ventricular-decline-correlates-well-with-other-forms-of-damage-in-the-aging-brain/

Here, researchers examine the correlation between ventricular dsyfunction, other noted forms of damage observed in brain aging, and the onset of cognitive decline. The ventricular system is where cerebrospinal fluid is created and circulates throughout the brain. Many things go wrong in the aging brain, all stemming from the same few root cause processes of damage accumulation in and around cells. Thus correlations between specific observed changes and the progression of dementia should be expected, but don't necessarily imply direct causation - though a particularly good correlation always indicates that further investigation is probably merited.

This line of investigation ties in to a growing area of research regarding the impairment of drainage of cerebrospinal fluid in aging. This impairment may explain the slowly rising levels of protein aggregates and other molecular waste in the brains of older individuals, a state of affairs known to contribute to the development of neurodegenerative conditions. Normally these wastes are removed at some pace through various filtration and drainage channels for cerebrospinal fluid, but the channels become dysfunctional, just like all other biological systems in older individuals. Leucadia Therapeutics is an example of a company working to intervene and restore youthful levels of drainage to what they consider the more important path. Other groups are looking into different areas of impaired fluid flow in the brain. All in all it is a most interesting and promising area of development.

The human brain's ventricular system is essential for the movement of nutrient-rich cerebrospinal fluid (CSF) throughout the central nervous system. A special epithelial lining along the ventricle walls composed of ependymal cells allows for the movement of CSF nutrients into the brain parenchyma as well as clearance of proteins and metabolites from the interstitial fluid (ISF). This ependyma-mediated bidirectional CSF-ISF exchange, as well as the formation of a cell barrier to prevent movement of proteins and metabolites from the CSF back into the ISF, relies on the presence of an intact ependymal cell monolayer. Pathological conditions in humans that are characterized by ependymal cell stretching and/or loss, including hydrocephalus, typically result in decreased CSF turnover rates and impaired clearance of proteins and metabolites resulting in a harmful buildup of these substances in brain parenchymal tissue.

Longitudinal magnetic resonance imaging (MRI)-based studies have established that expansion of the brain's fluid-filled lateral ventricles (LVs), or ventriculomegaly, is a defining feature of the aging brain. Ventricle expansion rates correlate strongly with declining cognitive performance and the rate of ventricle volume increase has been linked to an increase in Alzheimer's disease (AD)-related amyloid-beta (Aβ) plaques and tau neurofibrillary tangles, as well as alterations in CSF biomarker composition. Together, these point towards defective CSF-ISF exchange and impaired clearance mechanisms that are characteristic of AD.

Degeneration of periventricular brain tissue and declines in associated white matter tract integrity are common with normal aging and the extent of periventricular tissue abnormalities has been linked to dementia and AD. Periventricular hyperintensities (PVH), as measured using MRI, are indicative of fluid accumulation, or edema, often located in the parenchymal tissue directly adjacent to the frontal and occipital horns of the LV. The precise etiology of PVH is not clear; however, studies have implicated impaired drainage of ISF from the periventricular white matter resulting in aberrant fluid accumulation.

In previous studies, we found that enlarged ventricles from aging humans exhibited regional gliosis in the place of functional ependymal cell coverage. We predict that replacement of the ependymal lining with stratified layers of astrocytes at the ventricle surface adversely affects CSF/ISF bulk flow mechanisms, leading to fluid accumulation or edema and harmful buildup of proteins and metabolites in the periventricular space. Due to the rarity of longitudinal MRI data sets and associated subject-matched periventricular tissue biospecimens, this has never been directly demonstrated.

Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Baltimore Longitudinal Study of Aging (BLSA), we investigated the relationships among the following variables: ventricle expansion, PVH, periventricular white matter tract integrity, and degree of cognitive impairment. We also investigated the histopathological correlates of these measures, including LV wall gliosis and periventricular protein accumulation. We found that both LV and PVH volumes increase with age, and this expansion is more rapid and dramatic in cognitively impaired (CI) subjects. We also found a direct relationship between LV volume and PVH volume increase. Case studies from the BLSA allowed us to link ventricle expansion with regional gliosis, where an intact ependymal cell monolayer was replaced with stratified layers of astrocytes in regions of LV expansion. Additionally, adjacent parenchymal regions exhibited edema (as indicated by PVH), white matter deterioration, decreased vascular integrity, and harmful buildup of proteins including Aβ and tau.

Naked Mole-Rats Experience Cellular Senescence, but Seem Largely Unaffected by It
https://www.fightaging.org/archives/2018/02/naked-mole-rats-experience-cellular-senescence-but-seem-largely-unaffected-by-it/

Naked mole-rats are distinguished by an exceptionally long life span in comparison to similarly sized rodents, and a near immunity to cancer. Unlike other mammals, their mortality rates stay fairly constant until very late life. They accumulate all the signs of significant oxidative damage in cells and tissues, but seem resilient to it. Similarly, researchers here note that naked mole-rats do in fact accumulate senescent cells, one of the root causes of aging, but appear resilient to the harmful presence and activities of these cells. Exactly why this is the case has yet to be determined.

Cells become senescent in response to potentially cancerous damage or reaching the Hayflick limit on replication. The vast majority destroy themselves or are destroyed by the immune system, but a tiny fraction linger. They generate signals that spur chronic inflammation, change surrounding cell behavior for the worse, and destructively remodel nearby tissue structures. This results in functional decline in organs and other important tissues and systems. It is interesting to see that while there are differences in the detailed behavior of senescent cells between naked mole-rats and other mammals, they nonetheless still generate the same damaging signals, and yet the naked mole-rats appear to shrug it off.

With their large buck teeth and wrinkled, hairless bodies, naked mole rats won't be winning any awards for cutest rodent. But their long life span - they can live up to 30 years, the longest of any rodent - and remarkable resistance to age-related diseases, offer scientists key clues to the mysteries of aging and cancer. That's why researchers studied naked mole rats to see if the rodents exhibit an anticancer mechanism called cellular senescence.

Previous studies indicated that when cells that had undergone senescence were removed from mice, the mice were less frail in advanced age as compared to mice that aged naturally with senescent cells intact. Researchers therefore believed senescence held the key to the proverbial fountain of youth; removing senescent cells rejuvenated mice, so perhaps it could work with human beings. But is eliminating senescence actually the key to preventing or reversing age-related diseases, namely cancer?

Researchers compared the senescence response of naked mole rats to that of mice, which live a tenth as long - only about two to three years. Their unexpected discovery? Naked mole rats do experience cellular senescence, yet they continue to live long, healthy lives; eliminating the senescence mechanism is not the key to their long life span. The researchers found that although naked mole rats exhibited cellular senescence similar to mice, their senescent cells also displayed unique features that may contribute to their cancer resistance and longevity.

The cellular senescence mechanism permanently arrests a cell to prevent it from dividing, but the cell still continues to metabolize. The researchers found that naked mole rats are able to more strongly inhibit the metabolic process of the senescent cells, resulting in higher resistance to the damaging effects of senescence. "In naked mole rats, senescent cells are better behaved. When you compare the signals from the mouse versus from the naked mole rat, all the genes in the mouse are a mess. In the naked mole rat, everything is more organized. The naked mole rat didn't get rid of the senescence, but maybe it made it a bit more structured."

The Longest-Lived Bats Have Unusual Telomere Biology
https://www.fightaging.org/archives/2018/02/the-longest-lived-bats-have-unusual-telomere-biology/

Researchers here find that the longest lived bats have unusual telomere biochemistry, and in fact unusual enough that the new knowledge may turn out to be of little relevance to the understanding of telomeres, telomerase, and aging in other mammals. It appears that they rely upon alternative lengthening of telomeres (ALT) to maintain telomere length, a process that doesn't operate in any normal adult human cell. Given that loss of telomere length appears to be a marker of aging rather than a cause, and a fairly loosely coupled marker at that, the real relevance of this area of biochemistry probably lies in the relationship between telomerase and important cellular activities, such as ability and willingness of somatic cells to replicate, or stem cells to support tissue function.

Bats exhibit cellular biochemistry that is somewhat different from that of ground-based species in a number of other ways. The metabolic demands of flight have led to, for example, greater resilience to stress and damage arising from the normal operation of cellular metabolism. When charting life span against metabolic rate, where high metabolic rates usually imply short life spans, some small bat species are noteworthy outliers. Brandt's bat, for example, has a life span of four decades despite being the same size as ground-dwelling mammals that live for only a couple of years.

One of the principal caveats at the present stage of research into telomeres and the use of telomerase gene therapies - or other means of enhancing telomerase activity - as a treatment for aspects of aging is that mice and humans have quite different telomere dynamics and patterns of natural telomerase activity. The balance between cancer risk and beneficially increased stem cell activity resulting from telomerase therapies may turn out to be significantly different in different species. That these bats have their own unique evolved dynamics, ones that are much further removed, suggests that this portion of the comparative biology might not be as useful to the practical science of aging as hoped. The fastest path to understanding is probably to extend present work on telomerase therapies to species more like humans in their telomere biology, such as dogs and pigs perhaps. Or, as some advocate, running human trials immediately.

We urgently need to better understand the mechanisms of the aging process, with a view to improving the future quality of life of our aging populations. Most aging studies have been carried out in shorter-lived laboratory model species, given the ease of manipulation, housing, and length of life span. Although they are excellent study species, it is difficult to extrapolate experimental findings in these short-lived laboratory species to long-lived, outbred species such as humans. Therefore, it has been argued that long-lived, outbred species such as bats may be better models to investigate the aging processes of relevance to people.

Only 19 species of mammal are longer-lived than humans in proportion to their body size, and 18 of these species are bats. Bats are the longest-lived mammals relative to their body size, with the oldest bat recaptured (Myotis brandtii) being more than 41 years old, weighing ~7 g, and living ~9.8 times longer than predicted for its size. Although an excellent model species to study extended healthspan, logistically, it is difficult to study aging in bats because they are not easily maintained in captivity. Here, uniquely drawing on more than 60 years of cumulative long-term, mark-recapture studies from four wild populations of long-lived bats, we determine whether telomeres, a driving factor of the aging process, shorten with age in Myotis myotis (n = 239; age, 0 to 6+ years), Rhinolophus ferrumequinum (n = 160; age, 0 to 24 years), Myotis bechsteinii (n = 49; age, 1 to 16 years), and Miniopterus schreibersii (n = 45; age, 0 to 17 years).

We show that telomeres shorten with age in Rhinolophus ferrumequinum and Miniopterus schreibersii, but not in the bat genus with greatest longevity, Myotis. As in humans, telomerase is not expressed in Myotis myotis blood or fibroblasts. Selection tests on telomere maintenance genes show that ATM and SETX, which repair and prevent DNA damage, potentially mediate telomere dynamics in Myotis bats. Twenty-one telomere maintenance genes are differentially expressed in Myotis, of which 14 are enriched for DNA repair, and 5 for alternative telomere-lengthening mechanisms. These results, coupled with differential expression of ATM, SETX, MRE11a, RAD50, and WRN across all tissues in the genus Myotis compared to other mammals, suggest a potential role for alternative lengthening of telomeres (ALT) mechanisms in the maintenance of telomeres in these species. If telomeres are maintained by ALT mechanisms in Myotis species, then these genes may represent excellent therapeutic targets given that cancer incidence in bats is rare.

MDM2 Antagonists Attenuate Harmful Signaling from Senescent Cells
https://www.fightaging.org/archives/2018/02/mdm2-antagonists-attenuate-harmful-signaling-from-senescent-cells/

A fair number of the scientists working towards therapies to address cellular senescence, one of the causes of aging, are more interested in suppressing signaling from these cells than in destroying them. Cynically, a treatment one has to keep using consistently is much more interesting to pharmaceutical companies than a treatment that only has to be applied once every few years at most. Until researchers encounter a population of senescent cells that cannot be safely removed, destruction continues to look like the far better option. Senescent cells are harmful because of the mix of signals they generate, a mix that is still comparatively poorly mapped and understood. Suppressing it may well prove to be a lengthy and difficult process of progress by small degrees, while destruction can be achieved in the near future and removes all of the harmful signaling whether or not it is understood.

Astrocytes are one potential candidate for a population of senescent cells that might be challenging to remove. It isn't completely clear that all of the astrocytes showing markers of senescence are actually senescent, but if so it represents a large portion of all astrocytes in the aging brain. Abrupt clearance of these cells would probably not be healthy, regardless of the incremental harms they are causing. With this sort of thing in mind, it is prudent to have a backup strategy under development, whether that is some form of careful incremental winnowing and replacement of these cells over time, or a form of suppression of their bad behavior while allowing them to live.

One of the common features of aging is low-level chronic inflammation, termed sterile inflammation or inflammaging. Even though all the sources of inflammaging are unclear, it likely derives at least partly from senescent cells. Mammalian cells undergo senescence in response to stressful stimuli. An important feature of senescent cells is the secretion of a myriad of biologically active factors, termed the senescence-associated secretory phenotype (SASP).

The SASP is similar between mice and humans, and comprises inflammatory cytokines such as IL-6 and IL-8. The SASP can disrupt the surrounding microenvironment and normal cell functions, and stimulate malignant phenotypes in nearby cells. Senescent cells can also promote tumor growth in mice. Because senescent cells increase with age and are frequently found within hyperplastic and degenerative tissues, the SASP may be a major cause of inflammaging. Compounds that modulate the SASP hold promise for ameliorating a number of diseases of aging, including cancer.

Nutlins were originally identified as potent small molecules that inhibit the interaction between p53 and MDM2, which promote p53 degradation. Nutlin therefore stabilizes p53, thereby promoting the apoptotic death of cancer cells. Importantly, in cancer cells, nutlin-3a inhibits the activity of NF-κB, a potent transcriptional stimulator of genes encoding inflammatory cytokines, in a p53-dependent manner. The clinical importance of small-molecule MDM2 inhibitors like nutlin-3a spurred the discovery of similar compounds, such as MI-63, which are more efficient inhibitors of the MDM2-p53 interaction.

We investigated the effects of small-molecule MDM2-p53 interaction antagonists on senescent phenotypes, including the SASP, of primary human fibroblasts and epithelial cells. We used nutlin-3a, as well as the non-peptide small molecule inhibitor of MDM2, MI-63. We compared these compounds for their ability to induce a growth-arrested state, whether quiescence or senescence, in human cells, and evaluated their ability to modulate the SASP. We found that both compounds trigger selected markers of a senescent-like state, but the growth arrest was reversible, and both significantly suppressed the SASP, suggesting potential utility as therapeutic agents.

Mitochondrially Targeted Antioxidant SS-31 Improves Cognitive Function in Old Mice
https://www.fightaging.org/archives/2018/02/mitochondrially-targeted-antioxidant-ss-31-improves-cognitive-function-in-old-mice/

Oxidative damage has long been linked to aging, but the general use of antioxidants does nothing for life span. In fact, the evidence suggests this approach is modestly harmful, possibly due to blocking the oxidative signaling needed for exercise and other, similar mild stresses to produce benefits via hormesis. Antioxidant compounds targeted to the mitochondria are a different story, however, and have been shown to slow aging or partially reverse some aspects of aging in mice and lower animals - as is the case in this open access paper.

Mitochondria are the power plants of the cell, and generate reactive molecules that raise oxidative stress as a side-effect of the processes that produce chemical energy stores. This flow of reactive molecules influences the behavior of the cell in numerous ways; methods of slightly slowing aging have been demonstrated that either lower production, leading to less oxidative damage, or raise it, spurring increased maintenance activities in the cell. In the research here, benefits are derived indirectly: damping down oxidative damage improves the function of blood vessels in the aged brain, which helps to restore some degree of lost cognitive function in old mice. The brain is an energy-hungry organ, and age-related neurodegenerative conditions are characterized by a general decline in the capacity of of the blood supply and mitochondria in cells to supply as much energy as is needed.

Normal functioning of the central nervous system (CNS) requires a continuous, tightly controlled supply of oxygen and nutrients as well as washout of harmful metabolites through uninterrupted cerebral blood flow (CBF). The energetic demands of neurons are very high, yet the brain has very little energetic reserves. During periods of intense neuronal activity, there is a requirement for adjusting oxygen and glucose delivery to local neuronal activity through rapid adaptive increases in CBF. This is ensured by a mechanism known as neurovascular coupling (NVC). The resultant functional hyperemia is a vital mechanism to maintain optimal microenvironment of cerebral tissue and thereby ensuring normal neuronal function.

There is an increasing appreciation that (micro)vascular contributions to cognitive impairment and dementia in elderly patients are critical. Importantly, neurovascular coupling responses are impaired both in elderly patients and aged laboratory animals. Experimental studies support this concept, showing that pharmacologically induced neurovascular uncoupling in mice mimics important aspects of age-related cognitive impairment. On the basis of these findings, we proposed that novel therapeutic interventions should be developed to rescue functional hyperemia in elderly patients to prevent/delay cognitive impairment. Previous studies demonstrate that aging exacerbates generation of reactive oxygen species (ROS) in the cerebromicrovascular endothelial cells, which contribute to age-related neurovascular uncoupling in aged mice by promoting endothelial dysfunction. We hypothesize that pharmacological treatments, which attenuate endothelial oxidative stress, will have the capacity to improve neurovascular coupling in aged individuals.

The mitochondrial free radical theory of aging posits that mitochondria-derived ROS (mtROS) production and related mitochondrial dysfunction are a critical driving force in the aging process. In support of this theory, it was demonstrated that attenuation of mitochondrial oxidative stress (by mitochondria-targeted overexpression of catalase) increases mouse lifespan. There is particularly strong evidence that mitochondrial oxidative stress is implicated in cardiovascular aging processes. Yet, although drugs that improve mitochondrial function have been shown to exert beneficial effects both on the vasomotor function of peripheral arteries, their potential protective effects on the aged cerebral microvasculature has not been investigated.

This study was designed to test the hypothesis that pharmacological attenuation of mtROS can restore cerebromicrovascular endothelial function and thus improve neurovascular coupling in aged mice. To achieve this goal, in aged mice mitochondrial oxidative stress was manipulated by treatment with the mitochondrial-targeted peptide SS-31. We found that neurovascular coupling responses were significantly impaired in aged mice. Treatment with SS-31 significantly improved neurovascular coupling responses by increasing cerebromicrovascular dilation, which was associated with significantly improved spatial working memory, motor skill learning, and gait coordination. These findings are paralleled by the protective effects of SS-31 on mitochondrial production of reactive oxygen species and mitochondrial respiration in cultured cerebromicrovascular endothelial cells derived from aged animals.


View the full article at FightAging

Need help making sense of blood glucose readings

by @ ImmInst Active Topics

Hi!

I'm usually only reading at these forums but decided that I need some help to figure out what is going on with my blood glucose.

Fasting in the morning it is 75-83 mg/dL typically. After my typical breakfast (1l yogurt, some cottage cheese and a slice of bread or some oatmeal) the blood glucose looks like this:
Before breakfast 75
15 min post 75
1 hour post 65
2 hour post 65
3 hour post 84

Before lunch 80
45 min after lunch 85
75 min after lunch 78
110 min after lunch 97
2.5 hours after lunch 86

This lunch consisted of gluten free pasta (rice pasta)
Cottage cheese, meatballs

What I'm not getting is why my blood glucose drops to hypo range after breakfast, but not after lunch?

I do 16:8 IF

Supplements are:
Rhodiola,
Zinc carnosine for stomach issuer
Boron 10 mg
Lifeextension two a day multi @1 a day
B-right
Tmg
Omega 3 4g
L-tyrosine 800mg

All taken in the morning before breakfast.

I do heavy weight lifting twice a week.

Please comment and give advice to what is going on.

My suspicion so far is the high amount of dairy in the breakfast. I tried to reduce it bit with little effect. Im considering to omit it from breakfast. Other than that I dont know.

Thanks in advance

Best Ultimate Flora Probiotic Adults Best For Eczema

by @ Probiotics Belaw

Best Colon Cleansers of 2014. Colon cleansing tablets are used for weight loss and detoxification. Best Ultimate Flora Probiotic Adults Best For Eczema askville Question: I did a colon cleansing for a colonoscopy – is there a good over the counter method to periodically do th : Health The Colon Hydrotherapists Network. This colon cleanser […]

Hello !

by @ ImmInst Active Topics

Hi, I've come across the forum from time to time in my research of different supplements over the past couple years. Finally joined so I can add to some discussion and share my experiences as they happen. Cheers!

Write for LongeCity

by @ LongeCity - Articles

There are 4 ways of writing for LongeCity:

(1) Commissioned topics 
800-1500 word (ca. 2-3 pages) articles on any of the topics listed below. 
As long as the topic is listed, it remains open for submissions.
Authors are invited to submit a finished manuscript directly to caliban@longecity.org. Responses can be expected with 14 days after submission. 
Editors may require certain alterations for style, quality or based on peer-reviewed references, but publication is guaranteed for commissioned articles if the article meets a basic quality threshold.

(2) Submit an exposé for a new topic
You can send us a 200 word article outline, accompanied with a few lines about yourself. If accepted, you will be invited to submit a full article. 
Please use the contact form

Reward per published article: $180 (a premium may be awarded for particularly well-researched articles)

(3) Write a blog or (4) write on the forum
You can either start a blog at LongeCity or easily synchronise a blog that you maintain elsewhere. If your blog is consistently of interest and of good quality, you will automatically be awarded ‘Thank You’ points which can be redeemed for vouchers at online stores such as amazon. We might also ask you to do a regular column.
Thank you points also accrue to forum posts, as readers 'like' your posts. 

All articles and other written contribution are subject to the general LongeCity User agreement. In short authors keep full copyright of the article, but grant a free perpetual and worldwide license to LongeCity for non-commercial use. 



 -- current open commissions --

- ...
- Antioxidants: relevant for life extension?
- Brain transplantation: a medical impossibility?
- Cancer Risks in everyday products
- Cryonics: a scientific and technical description
- Current clinical trials particularly relevant to life extension
- DIYbio projects directed at life extension
- Gene Therapy: An update
- Heart attacks and strokes – emergency measures.
- Is advanced artificial intelligence the key to life extension?
- Lay diagnosis: spotting warning signs that could save your life
- Leaving Earth: seeding human life elsewhere
- Life extension enthusiasts of the 20th century: lessons for today
- Long term planning: trends and projections until 2200
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- Nanomedicine: recent advances
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- Profile: ‘XXX’ – a life extension pioneer
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- Supplements with a proven life extension benefit – any?

Costco Canada Unadvertised Deals of the week starting Feb. 12th

by Nadine @ Save Money in Winnipeg

Here are the deals from the Regent location in Winnipeg. Sales should be the same store to store, whether you’re in Saskatchewan, Alberta or British Columbia – Manitoba too of course! 🙂 And remember that Costco stores are closed next Monday (19th) across Canada for Family Day – so I’ll be posting on Tuesday. And […]

The post Costco Canada Unadvertised Deals of the week starting Feb. 12th appeared first on Save Money in Winnipeg.

Raw Probiotics Vitacost Myths Facts

by @ Probiotics Belaw

Kristina Amelong. Raw Probiotics Vitacost Myths Facts one of the best ways to do that is through a liver cleanse. When the body needs help Super Colon Cleanse is a powerful colon cleansing combination of herbs psyllium husk powder and milk-free acidophilus. This supplement is not as good as Colon Cleanse Total. Benefits of This […]

Why do some turtles outlive humans?

by @ Articles

(⇒ write for LongeCity )


The oldest human recorded in modernity was Jeanne Louise Calment, she died in the age of 122 years and 164 days [1] .

There are rumors that the oldest tortoise called Adwaita (Aldabra giant tortoise) died in the age of about 250 years [2] or that it was 188-year-old radiated tortoise named Tui Malila [3] , or that the highest verified age of 177 years had Galapagos giant tortoise Harriet [4] . The oldest currently living turtle is considered to be Jonathan (Seychelles giant tortoise), estimated to be over 180 years old these days [5] . Although all aforementioned numbers are estimations, it seems these turtles were older than human supercentenarians.

All previously mentioned species are terrestrial tortoises, a group with longest lifespans among turtles. The most famous of them, well-researched Galapagos giant tortoise, was observed by Charles Darwin when he was forming his well-known theory of evolution by natural selection [6] . There is only one freshwater turtle known to be able to outlive human, it is the common snapping turtle estimated to live up to more than hundred years [7] . While being considerably less researched, recorded maximal lifespan of sea turtles is usually shorter, not exceeding 80 years, however, it is believed that the green sea turtle can live up to 100 years. [8]

It is a difficult question to answer why these reptiles can outlive us because even to determine the actual age of animals with a long lifespan is complicated – partially due to the fact that it takes such a long time to study. Furthermore, many turtles are endangered species [9] so there may not be as many organisms to hand as needed for proper statistics. Nonetheless, we can still claim that turtles are among the most long-living vertebrates on earth [10] . Why?

Firstly, turtles, like all reptiles, benefit from being ectothermic organisms. They do not maintain body temperature and thus save a lot of energy. But that also means they are less flexible: it is crucial for their lifespan to be in natural temperature environment of daily cycles with night-time temperature drop [11] . If they do not live under these conditions in captivity, metabolic pathways change and turtles die much sooner. [12]

Turtles are well-adapted in other ways: their famous shell – the carapace –is good protection against natural predators. Most of hatchling turtles with a soft shell do not survive the first year [13] . A research of natural populations of freshwater turtles showed that only one per cent of them can celebrate the twentieth birthdays, but once the adulthood is reached, mortality rate drops and remains constant throughout the rest of life [14] .

Some turtles can survive under extreme environmental conditions, such as freezing [15] or lack of oxygen for months [16] . They can even undergo hibernation and anaerobic metabolism and therefore deal with hypoxia and anoxia, it was also proposed that the same genes can play a role in longevity itself [17] and also in oxidative stress resistance [18] that further promotes longer life [19] .

Turtle’s bones and shell are used as lactate buffer lowering metabolic acidosis caused by anaerobic glycolysis during the period of lack of oxygen [20] ; [21] Their organism is protected by strong innate immunity compensating slow acquired immune reactions [22] .

Because turtles have very slow metabolism as well as growth, their bodies do not need to deal with excessive metabolic heat and byproducts as mammals [23] . Their natural diet is very simple but also necessary for their longevity. [24]

According to the evolutionary theories, staying alive is less important after menopause. Galapagos giant tortoises achieve sexual maturity late (around the age of up to forty years in the wild, and between twenty and twenty-five years of life in captivity [25] ), then staying fertile until death [26] .

The Hayflick limit is said to determine how many times a cell can divide [27] . The Hayflick limit of Galapagos giant tortoise was said to be about 110 divisions [28] , approximately twice as many as 50 of human cells [29] . Studies in this context have highlighted the importance of telomeres, the protective end sequences of chromosomes, that get shorter with each cell division [30] , can play at least a partially role in life expectancy. It was observed that telomeres in European freshwater turtle’s cells are of the same length in both embryo and adult organism [31] .

Thus, it was believed that turtles are negligibly senescent organisms [32] . In other words, the cells do not age and no age-related diseases appear, which is very different cell behavior than in human bodies [33] and probably the key to any natural longevity. However, evidence now suggests that turtles may not be really negligibly senescent because of observations of survival and reproductive senescence in late age in the painted turtle population [34]

As we can see, turtles have some advantages in the lifespan field. Some of these might inspire researchers to increase lifespans in humans.



References

[1] Oldest person ever. Retrieved January 31, 2017, from http://www.guinnessworldrecords.com/world-records/oldest-person
[2] BBC (2006, March 23). “Clive of India’s” tortoise dies. BBC South Asia. Retrieved from http://news.bbc.co.uk/2/hi/south_asia/4837988.stm
[3] Associated Press (2006, June 26). Tortoise believed to have been owned by Darwin Dies at 176. Fox News. Retrieved from http://www.foxnews.com/story/2006/06/26/tortoise-believed-to-have-been-owned-by-darwin-dies-at-176.html
[4] Galapagos tortoise (Geochelone nigra) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Geochelone_nigra
[5] Hollins, J. (2012). The world’s most isolated vet? Veterinary Record, 171(2), i–i. doi:10.1136/vr.g7292
[6] Powell, J., & Caccone, A. (2006). Giant tortoises. Current Biology, 16(5), R144–R145. doi:10.1016/j.cub.2006.02.050
[7] Cameron, M. (2008). COSEWIC Assessment and Status Report on the Snapping Turtle Chelydra serpentina in Canada . Retrieved from http://publications.gc.ca/collections/collection_2009/ec/CW69-14-565-2009E.pdf
[8] Green sea turtle (Chelonia mydas) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Chelonia_mydas
[9] Jacobson, E. R. (1994). Causes of Mortality and Diseases in Tortoises: A Review. Journal of Zoo and Wildlife Medicine, 25(1), 2–17.
[10] Gibbons, J. W. (1987). Why do turtles live so long? BioScience, 37(4), 262–269. doi:10.2307/1310589
[11] Flouris, A. D., & Piantoni, C. (2014). Links between thermoregulation and aging in endotherms and ectotherms. Temperature, 2(1), 73–85. doi:10.4161/23328940.2014.989793
[12] Vadala, N. How Long Do Turtles Live? Retrieved January 31, 2017, from http://www.petmd.com/reptile/care/how-long-do-turtles-live
[13] Stewart, K. R., & Wyneken, J. (2004). Predation risk to loggerhead hatchlings at a high-density nesting beach in Southeast Florida. Bulletin of Marine Science, 74(2), 325–335.
[14] Gibbons, J. W., & Semlitsch, R. D. (1982). Survivorship and longevity of a long-lived vertebrate species: How long do turtles live? The Journal of Animal Ecology, 51(2), 523. doi:10.2307/3981
[15] Packard, G. C., & Packard, M. J. (2003). Natural freeze-tolerance in hatchling painted turtles? Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 134(2), 233–246. doi:10.1016/s1095-6433(02)00264-7
[16] Milton, S. L., & Prentice, H. M. (2007). Beyond anoxia: The physiology of metabolic downregulation and recovery in the anoxia-tolerant turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 147(2), 277–290. doi:10.1016/j.cbpa.2006.08.041
[17] Shaffer, H. B., Minx, P., Warren, D. E., Shedlock, A. M., Thomson, R. C., Valenzuela, N., … Wilson, R. K. (2013). The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage. Genome Biology, 14(3), R28.doi:10.1186/gb-2013-14-3-r28
[18] Garbarino, V. R., Orr, M. E., Rodriguez, K. A., & Buffenstein, R. (2015). Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates. Archives of Biochemistry and Biophysics, 576, 8–16. doi:10.1016/j.abb.2015.01.029
[19] von Zglinicki, T. (2002). Oxidative stress shortens telomeres. Trends in Biochemical Sciences, 27(7), 339–344. doi:10.1016/s0968-0004(02)02110-2
[20] Jackson, D. C. (2000). Living without oxygen: Lessons from the freshwater turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 125(3), 299–315. doi:10.1016/s1095-6433(00)00160-4
[21] Krivoruchko & Storey, 2010).
[22] Sandmeier, F. C., Tracy, C. R., Dupre, S., & Hunter, K. (2012). A trade-off between natural and acquired antibody production in a reptile: Implications for long-term resistance to disease. Biology Open, 1(11), 1078–1082. doi:10.1242/bio.20122527
[23] Bilinski, T., Paszkiewicz, T., & Zadrag-Tecza, R. (2015). Energy excess is the main cause of accelerated aging of mammals. Oncotarget, 6(15), 12909–12919. doi:10.18632/oncotarget.4271
[24] Casares, M., Honegger, R. E., & Rubel, A. (1995). Management of giant tortoises Geochelone elephantopus and Geochelone gigantean at Zurich Zoological gardens. International Zoo Yearbook, 34(1), 135–143. doi:10.1111/j.1748-1090.1995.tb00671.x
[25] Global, S. D. Z. (2010). Galapagos tortoise fact sheet. Retrieved January 31, 2017, from http://library.sandiegozoo.org/factsheets/galapagos_tortoise/tortoise.htm
[26] Curtin, A. J., Zug, G. R., & Spotila, J. R. (2009). Longevity and growth strategies of the desert tortoise (Gopherus agassizii) in two American deserts. Journal of Arid Environments, 73(4-5), 463–471. doi:10.1016/j.jaridenv.2008.11.011
[27] Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research, 37(3), 614–636. doi:10.1016/0014-4827(65)90211-9
[28] Goldstein, S. (1974). Aging in vitro. Experimental Cell Research, 83(2), 297–302. doi:10.1016/0014-4827(74)90342-5
[29] Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25(3), 585–621. doi:10.1016/0014-4827(61)90192-6
[30] Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345(6274), 458–460. doi:10.1038/345458a0
[31] Girondot, M., & Garcia, J. (1999). Senescence and longevity in turtles: What telomeres tell us. 9th extraordinary meeting of the societas Europaea Herpetologica, 1, 25–29. Retrieved from //www.researchgate.net/publication/252290006_Senescence_and_longevity_in_turtles_What_telomeres_tell_us
[32] Miller, J. K. (2001). Escaping senescence: Demographic data from the three-toed box turtle (Terrapene carolina triunguis). Experimental Gerontology, 36(4-6), 829–832. doi:10.1016/s0531-5565(00)00243-6
[33] Schächter, F., Cohen, D., & Kirkwood, T. (1993). Prospects for the genetics of human longevity. Human Genetics, 91(6), . doi:10.1007/bf00205074
[34] Warner, D. A., Miller, D. A. W., Bronikowski, A. M., & Janzen, F. J. (2016). Decades of field data reveal that turtles senesce in the wild. Proceedings of the National Academy of Sciences, 113(23), 6502–6507. doi:10.1073/pnas.1600035113

Costco Weekly Savings (Feb 12 - 18)

by couponlady @ SmartCanucks.ca Flyers, Deals Canada

*ON & Atlantic Canada: *Image: https://flyers.smartcanucks.ca/uploads/pages/98137/costco-weekly-savings-on-atlantic-canada-february-12-to-18-1.jpg ...

Too Much Probiotic Food Stool Hard

by @ Probiotics Belaw

True Cleanse Complete is designed to gently eliminate waste and toxins without Did you know studies have shown your colon to have eliminate waste and toxins without making your body feel miserable. Too Much Probiotic Food Stool Hard raw Food Vegan Recipes. Airmail to Europe (EU). Growing a baby is the most wondrous thing your […]

Sauerkraut Abnehmen Abends Smell Salad Enzyme

by @ Probiotics Belaw

V600E mutation is the most important to test. Maybe try the probiotics THOMAS DEKANY — Friday 7 April 2000 at 10:43 p.m. Sauerkraut Abnehmen Abends Smell Salad Enzyme these rare types are reviewed elsewhere. Consequently the recent discovery of putative biomarkers for colorectal cancer stem cells (CR-CSCs) is likely anterior resection sigmoid colon cancer cramps […]

trunature Digestive Probiotic: A Probiotic with 2 Beneficial Bacteria

trunature Digestive Probiotic: A Probiotic with 2 Beneficial Bacteria


PowerOfProbiotics.com

trunature Digestive Probiotic is a gluten-, dairy- and soy-free probiotic supplement with 10 billion CFU of beneficial bacteria per capsule.

Best Probiotic Strains For Constipation Tnm Classification Cancer

by @ Probiotics Belaw

GNLD’s Acidophilus Plus is the probiotic product for those who are lactose intolerant! Agricultural chemicals and pollution. Best Probiotic Strains For Constipation Tnm Classification Cancer in all drugs closing the orthodox government was even counted as an documentation. before your meal drink 2 glasses Replenishing your beneficial bacteria and yeast (Probiotics) will help you digest […]

Costco Canada Coupons of the week

by Nadine @ Save Money in Winnipeg

Lots of coupons starting this week at Costco – you can get the flyer in store or check them all out online too. There’s $3 off Rice Krispie treats, $4 off french onion soup, $4 off Purex, up to $40 off mattress toppers, and a lot of health and beauty ones too, including $6.50 off […]

The post Costco Canada Coupons of the week appeared first on Save Money in Winnipeg.

Probiotic Capsule Douche Taking Leaky Gut

by @ Probiotics Belaw

Sundown Naturals Inulin Fiber Prebiotic Mineral Supplement Capsules 90 Count $8.79 ($0.10 / count). Probiotic Capsule Douche Taking Leaky Gut seaman NEW YORK (Reuters Health) – Taking “good” bacteria known as probiotics may help prevent diarrhea ought on by a tough-to-treat infection that often results from taking antibiotics according to a fresh look at some […]

New Printable Coupon To Save $3 On Align Products On UniPrix

New Printable Coupon To Save $3 On Align Products On UniPrix


Free Mail & Discount Printable Coupons In Canada

A new align printable coupon to save $3 on your regular priced purchase of align products. For more printable coupons in canada enter here...

Help me choose a probiotic for histamine intolerance issue - Supplements

Help me choose a probiotic for histamine intolerance issue - Supplements


LONGECITY

Help me choose a probiotic for histamine intolerance issue - posted in Supplements: Wow, I thought all probiotics were the same.Had no idea there were so many choices.  I believe I have a histamine tolerance issue (rash around eyes when drinking alcoholic or fermented beverages(Kombucha) ao am looking for a probiotic that helps to suppress histamines. My understanding is that most yogurt and probiotics have just the opposite effect.After reading several articles I believe I need a pr...

How To Make Homemade Probiotic Drink Good Acidophilus For Is Bv

by @ projectathena probiotics composition

Every day the good natural flora in your body is killed off by stress junk food medications chlorinated water and a toxic environment. Use with Stop-it Smoking lozenges as directed by the program chart. How To Make Homemade Probiotic critical care probiotics natural factors difference normal yogurt between Drink Good Acidophilus For Is Bv oil […]

Homemade Mead – GAPS Approved

by Becky Plotner @ Nourishing Plot

Making mead is easy, delicious, festive and a great probiotic food to add to your probiotic food choices. Mead can be made several different ways. Using local honey is the easiest as it takes two simple ingredients: honey and water. There is no absolute way to make mead, the ratio of honey to [...]

The post Homemade Mead – GAPS Approved appeared first on Nourishing Plot.

Longecity Blog - win$100 for 'best regimen'

by @ LONGECITY Community Blog List

The forum structure at the heart of LongeCity works well in facilitating a free flow of communication and information exchange.
Other more structured ways of curating information have their own advantages, but their adoption appears to be more difficult.

 

In 2014 we closed the 'regimen' forums for brain enhancement and general supplements in favour of a new 'stacks' function.
aiming to generating a searchable database of combinations as an easily accessible resource.

 

It took some time for the new feature to gain traction. In some areas this worked ok, in others we still don't have any entries.

 

To further promote the feature we are launching a small COMPETITION for the BEST REGIMEN in each category.

 

On Sept.1st LongeCity leadership will draw up a shortlist of the most promising entries for each existing category:

  • Life Extension, General Health;
  • Alertness, Cognition, Mood
  • Sports, Performance, Bodybuilding
  • Medical
  • Weight Loss
  • Beauty, Cosmetics, Skin, Anti-Aging
This shortlist will be based (but not necessarily bound) by the average of the "star ratings" an entry has received from all LongeCity readers!
The Immortality Institute Members will then vote on a winner from each shortlist
The winner in each category* will receive $100 (via paypal) and 100.

 

(* yes, that means that the winning chance in the currently empty, or sparsely populated categories might be higher)

 

At least for the duration of the competition, the old 'stacks' forums will re-open. We hope that by now everyone has understood the distinction we are aiming for: the 'regimen' feature is for presenting and discussing structured regimens that can be considered, compared and potentially adopted by others down the ages, the forums are for more free-wheeling conversation that might be more speculative, protracted and less likely to hold a swift take-away message for others.

Colon Cancer X Ray Pictures Cancer Rates Survival Country

by @ projectathena probiotics composition

Anaemia (low number of red blood cells). probiotics.other than that i have to shove those things as well (Keep Prep Sheet In Bathroom For Your Reading Pleasure AND look this over . Colon Cancer X Ray Pictures Cancer Rates Survival Country i am having bad stomach aches and back pain for some time now. Drinking […]

Jagged-1 as a More Selective Signal to Spur Bone Regrowth

by @ LongeCityNews

Researchers here report on a more selective way to trigger the accelerated or enhanced regeneration of bone tissue, delivering jagged-1 to injuries rather than the bone morphogenetic proteins (BMPs) that have been used in the past. It appears to cause fewer issues related to inappropriate excess bone growth, as it influences mechanisms that are more closely associated with the process of regeneration in response to damage. The delivery of signals rather than cells or pharmaceuticals to produce regeneration will be a growing theme in the years ahead, and the approaches will only grow in sophistication and degree of control. The advance here is a small step in the grand scheme of the possible and the plausible; it will be interesting to see how this part of the industry evolves over the next few decades.

When a patient breaks a bone, there's a possibility the fracture won't heal properly or quickly, and use of a restorative tactic known as bone morphogenetic proteins, or BMPs, is increasingly less likely. Designed to promote spinal fusion and bone repair more than a decade ago, these molecules can overperform, causing excessive or misdirected bone growth, studies have shown. But because bone-healing biological research has often been limited, few other options exist. "Novel therapies have gone underdeveloped because of this assumption that bones heal without problem. The reality is there's a huge number of fractures that occur each year that don't heal very well."

The divide recently inspired scientists to examine a new therapeutic approach. Their method: deliver additional Jagged-1 - a potent osteoinductive protein known to activate the Notch signaling pathway that regulates bone healing - at the spot of a bone injury. "We've hypothesized for many years that by binding the Jagged-1 to a biomaterial and delivering it to a bone injury site, we could enhance healing." The results affirm that hunch: Rodents that received Jagged-1, applied via wet collagen sponge, saw improvements to skull and femoral bone injuries. Rodents treated with BMPs, by contrast, also benefited but developed the same problematic bone hypertrophy associated with human use of those proteins. Those findings suggest that the former therapy could one day benefit people.

It's not fully known why some bones don't heal the way they should - nor do scientists know whether a genetic component plays a role. What researchers have studied for years, meanwhile, is the capacity of the Jagged-1 ligand to promote bone-forming cells. The signaling is unique because this particular ligand typically binds to a delivery cell to activate bone healing in an adjacent cell - a vital trait to help ensure that a supplemental Jagged-1 dose, administered at the spot of injury, stays in place (and on task) to carry out its intended function. As a result, bone will only form where bone is supposed to form. BMPs, by comparison, are soluble, so they can migrate from the site of delivery and settle elsewhere in the body, triggering other cells that aren't supposed to form bone.

Link: https://labblog.uofmhealth.org/body-work/boosting-a-key-protein-to-help-bones-wont-heal


View the full article at FightAging

Probiotic Yogurt On Skin Oz Usana Dr

by @ Probiotics Belaw

A sluggish liver can lead to serious fatigue weight gain water retention and a host of other health woes. AIM Herbal Fiberblend is the only product I’ve tried that gets the black stuff out without fasting.” Unlike an enema it does not involve the retention of water just a steady gentle flow in and out […]

Community Testing of Aging Bio-Markers

by @ Action

Legitimate bio-marker testing is important to our community to help determine what current approaches are the best for slowing aging

 

It is 2018, and I can't believe how many anecdotal placebo-driven reports populate the LongeCity forum. Here is one egregious recent example if you want to chuckle: http://www.longecity.org/forum/topic/99447-hello-everybody-im-the-longest-continuous-user-of-hgh-in-human-history/

 

There was a budgeted effort to promote legitimate bio-marker testing last year, but it required members to pay for their first test, before embarking on an anti-aging regimen, where at the conclusion of the regimen time period, LongeCity would pay for a second test.

 

I am proposing a simpler approach. Here is the outline:

 

1. LongeCity pays for a standard aging-biomarker test. The most cost effective, easy to implement, and robust test available today is probably DNA methylation. LongeCity has a current relationship with Osiris Green and their test is the cheapest on the market, however, the standard deviation on their test is +/- 5 years. I have spoken with ZYMO and they will offer their test "at cost" for an effort such as this. ZYMO is HIPPA compliant and their standard deviation is only +/- 1.7 years.

 

2. We aim to offer this as a member benefit and to engage other communities such as the calorie restriction society.

 

3. Test subjects can opt to remain anonymous.

 

4. A simple questionnaire accompanies each test. This would ask each subject to rank their general approaches to life extension. Supplements, Diet, Exercise, Other. Depending upon the response, we could drill down further into regimens, but I would want to keep it simple at first to ensure a larger response.

 

5. We aim to complete the study before the end of Summer 2018, and present findings at RAADFest in September.

 

6. Stretch goal: Have a small number of people do DNA methylation testing at 3 different times of day. It is currently unknown if there is inter-day variability in DNA methylation.

 

7. Perhaps work in conjunction with newly formed OpenCures to complete and promote the study.

 

8. If successful, continue with testing on an annual or semi-annual basis. preferably with the same study participants.

 

Drawbacks/Objections

 

1. There are already a lot of groups (example: patients like me) that share test data, and there are many studies involving aging bio-markers. However, I am unsure that there are any studies that have easily accessible data AND focus upon longevity activists.

 

2. It is unlikely that a small study of a few dozen people will produce statistically valid results. To me, that is okay. We WILL learn something and I am certain there will be incredible marketing and community-building opportunities with such a study.

 

3. Cost. 5-10K, maybe higher if we can get some other groups to promote the study or if we can use other crowd-funding platforms. With 10K we could test between 50 and 75 people.

 

Leadership: I would be lead organizer and promoter.

 

LongeCity certainly has the budget for such a study and has enough connections to get a good number of people involved. LongeCity has not done much of consequence as of late. This could be a solid effort to help the community, not only functionally (what regimens work), but also as a promotional effort (life-extensionists are younger and healthier). 

 

 

Legitimate bio-marker testing is important to our community to help determine what current approaches are the best for slowing aging

LongeCityNow_Kelsey_Moody_2017

by @ Last 10 Submissions RSS Feed

A 2017 interview with the CEO of Ichor Therapeutics - Kelsey Moody. Topics range from the business of rejuvenation, AMD research, and C60 as a supplement.

Gaps Diet Without Probiotics Smits Jimmy Does Cancer

by @ projectathena probiotics composition

For long-term health and performance I add probiotics vitamin E selenium and mixed-carotonoids and also include a Grab the whole foods and then ditch the junk foods. Gaps Diet Without Probiotics Smits Jimmy Does Cancer liver detox a great way to purify their hearts of all poison is available in the body. probiotics for cats […]

Probiotic Deficiency Brands Yogurt Are What

by @ Probiotics Belaw

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by @ Probiotics Belaw

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WAPF’s and GAPS’ Current Response on FCLO, Years Later

by Becky Plotner @ Nourishing Plot

The current stance on the most recent Fermented Cod Liver Oil (FCLO) findings and accusations were announced at the 2017 Annual Weston A. Price Conference in Minneapolis, Minnesota on November 19th. 

{This post may contain affiliate links which pay for this site}.

In 2015 there was a big attack on fermented cod liver oil. [...]

The post WAPF’s and GAPS’ Current Response on FCLO, Years Later appeared first on Nourishing Plot.

Opinions on Weight Loss - Could policy revisions lead to a healthier nation?

by @ LONGECITY Community Blog List

So, I was reading this over at the FDA and it dawned on me that these safety side effects were only likely to occur in people who are aged. In young people, it would very likely not be an issue. So here's the bigger issue:

 

If you take these away from young people or dissuade them from using them altogether, the young people will lose the opportunity to be healthy. Could it be policies like these that are fattening up America while Japan enjoys the slimmest healthiest lifestyle the world over?

 

Instead, I propose that we put age limits on supplements like these. We have minimum ages for alcohol and tobacco, so why not require carding for maximum ages and put in place a system to allow regulatory authorities to print a max age code on retail boxes and bottles. This of course leaves the looming problem of agism still at play and these regulations may negatively impact those who grow younger, but we can cross that bridge when we get there. For now, we just need to ensure that young people don't get fat and that those who are unfortunate enough to be fat when young can get to their optimum weight and experience that while they are still young.

crowdsourced multivitamin

by @ Articles - Articles

Extending maximum human lifespan will likely require a wide range of new biotechnology. Powerful interventions such as pharmaceuticals, stem cell technology, and gene therapy are in development but could be years or decades away from widespread implementation. During the intervening time the best way to ward off the ravages of disease and aging is to take care of yourself.

Members of LongeCity are keenly aware of this reality. That is why LongeCity forum discussions about exercise, nutrition, and supplements are very active and comprehensive. Members are constantly on the lookout for the latest research lending insight into which supplements are beneficial, cost-effective, and readily available.
Much has been made of the deficiencies of current multivitamin formulations and this has led to a community effort to design the “perfect multivitamin”.


In a long process of collaborative discussion, Members designed what in their view comes closer to the 'perfect' anti-aging supplement than any other product on the market.
LongeCity then found a partner in RevGenetics Ltd (FDA RegNo: 12757922694) to produce it.

Under the brand name VIMMORTAL the formula was promoted during 2011.Many members enjoyed the heavy discount that RevGenetics generously provided to LongeCity members.

After over a year of sales, members decided to revisit the formula. The inclusion of choline in particular proved controversial in light of current research. VIMMORTAL was stopped and a new group convened to collate suggested tweaks and improvements. The revised formula was relayed to the previous partner Revgenetics.

After many delays and extensions throughout 2012, it became clear eventually that Revgenetics was not going to take the second generation of the crowdsourced supplement further.
This is a setback for the project, in which LongeCity was at the forefront of connecting supplement sellers and consumers in an innovative dialogue at the cutting edge of nutritional supplement design. However, we are proud of this effort and the experience and data generated by it.

The VIMMORTAL formula is 'open source' and we are optimistic that another manufacturer/seller will see the opportunities of connecting directly with the life extension community to provide the 'ideal' supplement solution.

Check the Vimmortal project forum.

Post lyme disease treatment advice...diet, bpc 157 and or?

by @ ImmInst Active Topics

Hey everyone,

Thank you in advance for taking the time to read and respond to my post. I’m a 23 year old (otherwise healthy) male who was diagnosed with lyme disease about two months ago. After undergoing an intense supplement/herbal/energetical therapy cleanse and detox, my docotor confirmed that the lyme had left my body. However, I am still experiencing all of my original symptoms, including random shaking, a neck tremor, intense brain fog, a really infammed gut/liver/kidneys, etc. I’m struggling to determine my next course of action — has anyone reading his post dealt with lyme? — have you tried dietary changes to help heal your system? I’m also curious if bpc 157 would be a good option for me? I already eat a fairly well balanced diet that is exclusively organic/non gmo, as well as taking about 15 relevant supplents a day (including probiotics). I guess, in general, I’m seeking any lyme, dietary, or other advice that you might have for me.

Thanks for your time,

-Braden

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by @ projectathena probiotics composition

What is Colorectal Cancer? How well does Eloxatin work in treating colorectal cancer? ovarian cyst and abdominal pain (3 replies): Colon Cancer can affect anyone at any age. Prevent and treat inflammation following colon surgery. Probiotics Infant Good probiotic probiotic cure gastritis medicine alternative cultures transplant in gi plantarum l. bacteria For Colitis lEBANESE INTERNATIONAL […]

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by @ projectathena probiotics composition

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Nootropics in human trials (Intro)

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The word "nootropic" derives from the Greek words nous, or "mind", and trepein meaning "to bend or turn". It was first coined by Romanian psychologist and chemist, Corneliu E. Giurgea after synthesizing Piracetam.
For Giurgea a nootropic drug should have the following characteristics:
1. They should enhance learning and memory.
2. They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3. They should protect the brain against various physical or chemical injuries (e.g. barbiturates, scopalamine).
4. They should increase the efficacy of the tonic cortical/subcortical control mechanisms.
5. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

In fact, most drugs commonly labelled as nootropics do not fulfill all of these requirements. Some of the best known (e.g. Adderall, Modafinil) seem to not fulfill any, as discussed later. Instead, other characteristics like (reputed increased alertness, focus or motivation) seem to be key to their popularity.
Because of deviating definitions nootropics are more broadly defined (e.g. in wikipedia) as drugs, supplements, or other substances that improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals. 

Some nootropics from the very common to the :

Caffeine
Caffeine is the world’s most widely used stimulant (Nawrot, et al., 2003). It is used by over 90 % of North Americans every day (Mednick et al., 2008). It is widely used because of its positive effects on mood and alertness (Lorist & Tops, 2003)and vigilance and attention (Lieberman et al., 1987). However, these effects do not seem applicable / transferable to motor learning and verbal memory and are unable to reverse effects of sleep deprivation, with a dose of 200mg in low to moderate users (< than 2 cups a day) (Mednick et al., 2008). It is also shown to be ineffective in higher cognitive tasks involving working memory (Battig et al., 1984). Overall conclusions regarding the relation of caffeine and memory have been mixed. Positive effects might stem from caffeine withdrawal in high dosage users (Mednick et al., 2008).

Nicotine
With about 1,1 billion smokers worldwide in the year 2015 (WHO 2015) nicotine takes second place as the most widely used stimulant. It was shown that the application of nicotine in non-smoking males enhances performance in continuous performance tasks and therefore is said to improve attention and working-memory (Kumari, et al., 2003), which is in line with other studies suggesting that nicotine affects short-term memory in delayed free recall tasks (Sarah & Fox, 1998)
Another study examined nicotine’s effects on alertness and performance on a covert orienting task were measured. While nicotine decreased overall reaction times in the covert orienting task, there was no change in the validity effect, the reaction time difference between validly and invalidly cued targets. However, nicotine significantly improved both EEG and self-rated measures of alertness. Nicotine seems to increases alertness in non-smokers, with no improvement in spatial attention using a covert orienting task (Griesar et al., 2002). Furthermore Nicotine seems to reduce distraction under low perceptual load by acting as a stimulus filter that prevents irrelevant stimuli entering awareness (Behler et al., 2015).

Methylphenidate/ Ritalin
Most college students I know will immediately think of Ritalin or Modafinil if they are asked to name a cognitive enhancer. Studies have found that 4.1% to 10.8% of college students in the US reported using prescription stimulants non-medically during the past year (Garnier-Dykstra, et al., 2012).
Methylphenidate (MPH - common brand name ‘Ritalin’) is used in treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Most studies focused on the its effects on Attention, Mood, Memory and executive functions. A single dose of MPH showed a positive effect on memory. Repeated doses of MPH had a mood elevating effect but also enhanced anxiety. No statistically significant effect was found in the outcomes attention, mood and executive functions. MPH had no significant effect on sleep-deprived individuals (Repantis et al., 2010). In a 2015 review the authors found some ‘publication bias’, relating to long-term and working memory and conclude that the effect in healthy subject is probably modest overall and that healthy users resort to stimulants to enhance their energy and motivation more than their cognition (Ilieva et al., 2015). 

Modafinil
Modafinil is used in treatment of disorders such as narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Most studies focused on its effects on attention, mood, memory, wakefulness and executive functions and motivation. A single dose showed positive effects on attention only. On sleep deprived individuals it was shown to have an impact on executive functions, on memory and wakefulness but there was an insignificant effect on mood and attention (Repantis et al., 2010). A 2012 meta-analysis found that Modafinil was likely effective but criticised the gaps in the literature. (Kelley et al., 2012) 
A recent study on chess players found significantly enhanced performance with Modafinil or Ritalin but only when the players were not under time pressure (Franke et al. 2017). 

Adderall
Mixed Amphetamine Salts also known under the brand Name Adderall became increasingly popular in recent years as an athletic performance enhancer and cognitive enhancer. Like Ritalin, it is also used to treat ADHD and narcolepsy.
Overall effects of Adderall on cognition have been reviewed as very modest, while having a huge effect on perception. It was found to enhance performance in word recall, embedded figures and Raven's Progressive Matrices, but only for lower performing individuals (Ilieva et al., 2013). Adderall might also impair creativity in high performing individuals (Farah et al., 2009).

L-theanine & Caffeine
L- theanine is primarily found in plants (e.g. in the leaves of green and black tea) and fungus. Results evidently demonstrated that L-theanine clearly has a pronounced effect on attention performance and reaction time response in normal healthy subjects susceptible to having high anxiety (Higashiyama et al., 2011).
A dose of L-theanine equivalent to eight cups of black tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. The combination of Theanine and caffeine seem to have additive effects on attention in high doses (Kahathuduwa et al.,2016).
Studies suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task (Giesbrecht 2010).

Bacopa Monnieri
Bacopa Monnieri is an herb which has been used in Ayurvedic medicine for centuries. Bacopa's primary mechanism of action is still unclear, it seems to be an anti-oxidant, a weak acetylcholinesterase inhibitor and a cerebral blood flow activator (Aguiar & Borowski , 2013).
There is some evidence to suggest that Bacopa Monnieri improves memory with little evidence of enhancement in any other cognitive domains (Pase et al., 2012).

Piracetam
Closing the circle to the beginning of this short introduction to the topic: Giurgea first coined the term "nootropic" when he synthesized Piracetam in 1964. Since it is not approved by the US FDA, it is primarily used in Europe, Asia, and South America. It is commonly prescribed for cognitive impairment and dementia in several countries of Europe. Research suggests that Piracetam might also have a positive effect on healthy individuals. Subjects were given 3×4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased (Dimond & Brouwers, 1976). It might also be beneficial for cognitive decline associated with age. Aging subjects did significantly better in a computerized perceptual-motor tasks when on piracetam than on a placebo. (Mindus et al. 1976). While these old studies may not be that reliable, it is still held that Piracetam's “efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated” (Winblad, 2005). Since Piracetam was first synthesized many structurally similar compounds have emerged. These so called Racetams have poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems (Gualtieri et al., 2002).


This article is solely for information purposes, not a substitute for professional medical or dietary advice. 
The provisos of the LongeCity user agreement apply.

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References
* Aguiar, S., & Borowski , T. (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research, 313-326. 
* Battig , K., Martin, J. R., & Feierabend , J. M. (1984). The effects of caffeine on physiological functions and mental performance. Experentia, 1218–1223.
* Behler , O., Breckel, T. P., & Thiel , C. M. (2015). Nicotine reduces distraction under low perceptual load. Psychopharmacology, 1269-1277.
* Dimond, S. J., & Brouwers, E. M. (1976). Increase in the power of human memory in normal man through the use of drugs. Psychopharmacology, 307-309.
* Farah , M., Haimm , C., Sankoorikal , G., Smith , M., & Chatterjee , A. (2009). When we enhance cognition with Adderall, do we sacrifice creativity? A preliminary study. Psychopharmacology,541-547.
* Franke, A.G.; Gränsmark, P., Agricola, A., Schühle, K., Rommel, T., Sebastian, A., Balló, H.E., Gorbulev, S., Gerdes, C., Frank, B., Ruckes, C., Tüscher, O., Lieb, K. (2017) "Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial" in: European Neuropsychopharmacology Vol27, Issue 3, 1, pp248-260
* Garnier-Dykstra, L. M., Caldeira, K. M., Vincent, K. B., O’Grady, K. E., & Arria, A. M. (2012).Nonmedical use of prescription stimulants during college: Four-year trends in exposure opportunity, use, motives, and sources. J Am Coll Health, 226-234.
* Giesbrecht, T., Rycroft , J. A., Rowson , M. J., & De Bruin , E. A. (2010). The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutritional Neuroscience, 283-290.
* Griesar , W. S., Zajdel , D. P., & Oken , B. (2002). Nicotine effects on alertness and spatial attention in non-smokers. Nicotine & Tobacco Research, 185-194.
* Gualtieri , F., Manetti , D., Romanelli , M. N., & Ghelardini , C. (2002). Design and study of piracetamlike nootropics, controversial members of the problematic class of cognition-enhancing drugs. Current Pharmaceutical Design, 125-138.
* Higashiyama, A., Htay, H. H., Ozeki, M., Juneja, L. R., & Kapoor, M. P. (2011). Effects of l-theanine on attention and reaction time response. Journal of Functional Foods, 171-178.
* Ilieva, I., Boland, J., & Farah, M. (2013). Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people. Neuropharmacology, 496-505.
* Ilieva IP, Hook CJ, Farah MJ. (2015) Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis.; J Cogn Neurosci. 2015 Jun;27(6):1069-89. 
* Kahathuduwa, C. N., Dassanayake , T. L., Amarakoon , A. M., & Weerasinghe, V. S. (2016). Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutritional Neuroscience.
* Kelley, A.M.; Webb, C.M., Athy, J.R., Ley, S., Gaydos, S. (2012) "Cognition enhancement by modafinil: A meta-analysis" in Aviation Space and Environmental Medicine; Vol83, Issue 7, p685-690
* Kumari, V., Gray, J., H ffytche, D., Mitterschiffthaler, M., Das, M., Zachariah, E., . . . Sharma, T. (2003). Cognitive effects of nicotine in humans: an fMRI study. NeuroImage, 1002-1013.
* Lieberman , H. R., Wurtman, R. J., Emde, G. G., Roberts , C., & Coviella, I. L. (1987). The effects of low doses of caffeine on human performance and mood. Psychopharmacology, 308-312.
* Lorist , M. M., & Tops, M. (2003). Caffeine, fatigue, and cognition. Brain Cognition, 82-94.
* Mednick, S. C., Cai, D. J., Kanady, J., & Drummond, S. P. (2008). Comparing the benefits of Caffeine,Naps and Placebo on Verbal, Motor and Perceptual Memory. Behavioural Brain Research, 79–86.
* Mindus , P., Cronholm , B., Levander , S. E., & Schalling , D. (1976). Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. Acta Psychiatrica Scandinavia, 150-160.
* Nawrot, P., Jordan, S., Eastwood , J., Rotstein , J., Hugenholtz, A., & Feeley, M. (2003). Effects of caffeine on human health. Food Additives & Contaminants, 1-30.
* Pase, M. P., Kean , J., Sarris , J., Neale , C., Scholey , A. B., & Stough , C. (2012). The cognitive enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. Journal of Alternative Complementary Medicine, 647-652.
* Repantis , D., Schlattmann , P., Laisney , O., & Heuser, I. (2010). Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacological Research, 187-206.
* Sarah , P., & Fox, P. (1998). An investigation into the effects of nicotine gum on short-term memory.Psychopharmacology, 429-433.
* WHO (2015). WHO global report on trends in tobacco smoking 2000-2025. WHO Library Cataloguing-in Publication Data .
* Winblad, B. (2005). Piracetam: a review of pharmacological properties and clinical uses. CNS Drug reviews, 169-182.

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