Bluebonnet Probiotic Acidophilus Plus FOS Review
by Kate Watson @ ProbioticsGuide.com
Wed Jan 24 21:58:50 PST 2018
Detailed review of Bluebonnet Probiotic Acidophilus Plus FOS. See how this probiotic supplement compares against all the others!
The post Bluebonnet Probiotic Acidophilus Plus FOS Review appeared first on ProbioticsGuide.com.
Justin Trudeau calls for acknowledgement of anti-black racism in Canada
by @
Mon Feb 12 19:01:00 PST 2018
Justin Trudeau says it's time Canadians acknowledged that racism and unconscious bias against black people exist in this country.
Nootropics in human trials (Intro)
by @ Articles
Sat Sep 09 06:57:38 PDT 2017
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. |
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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Do Probiotics Help With Mood Plants
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The 7 Best Prebiotic Foods You Need In Your Diet
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Fri Dec 08 13:16:30 PST 2017
Are you struggling with getting your daily dose of prebiotics? Just add these 7 key prebiotic foods into your diet! Click now to find out what they are…
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Thunder Bay, Ontario
by Renew Life @ Renew Life Canada
Wed Aug 31 08:18:05 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
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CTVNews
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Well
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by Renew Life Team @ Renew Life Canada
Tue Sep 20 13:38:19 PDT 2016
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Popular Probiotic May Cause Neurotoxicity
Mommypotamus
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Is There Gluten in Your Probiotics? - Web Only Articles
Gluten Free & More
A small study presented earlier this month at the annual Digestive Diseases Week meeting reports there may be trace amounts of gluten in some probiotics. A lot of people with celiac disease and gluten sensitivity take probiotic supplements for digestive health. In this study, researchers sampled 22 popular probiotic brands, including 15 that were labeled gluten-free. Half of them contained detectable amounts of gluten, with two brands containing more than 20 parts per million (ppm) of gluten, the threshold set by FDA for gluten-free labeling.
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Detailed review of ProBiome Rx Leaky Gut Formula. See how this probiotic supplement compares against all the others!
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Why do some turtles outlive humans?
by @ Articles - Articles
Wed Feb 08 16:45:06 PST 2017
(⇒ 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
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A List Of The Best Commercial Probiotics » The Candida Diet
The Candida Diet
How do you choose a good probiotic? This page contains a table of more than 80 commercial probiotics, along with all the information you need on each one.
Raw Probiotics Vitacost Myths Facts
by @ Probiotics Belaw
Sun Jan 07 15:15:19 PST 2018
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 […]
Baby Gourmet Contest: Win a Baby Gourmet product sampler -New
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 16:01:47 PST 2018
NEW Baby Gourmet Contest for Canada 2018 Enter to win a Baby Gourmet product sampler. Simply leave a comment on either the facebook or instagram post ,answering the question to win. Good Luck. Rules Open to Canadian residents only Excludes Quebec Ages 18 and older Valid facebook OR instagram account Single entry per social media Enter […]
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American states look to lower drug costs, consider Canadian imports
by @ CTVNews.ca - Health - Public RSS
Sun Feb 11 17:36:52 PST 2018
Lawmakers in more than two-thirds of the states are considering ways to reduce prescription drug costs, including importing them from Canada, as they strive to balance budgets without knowing for sure what their government’s share of the tab will be.
KFC Deals from Colonel’s Club valid February 12-18, 2018
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 05:44:39 PST 2018
Kentucky Fried Chicken – KFC Deals For Canada Colonel’s Club Only – Exclusive Savings: for 2018 Family Meal Deal: $10 off 25pc Party Pack Individual Meal Deal: $13.25 for 2 Can Dine Big Crunch Combo How to use: Use your Club Card In-store to get your KFC Deals and saving. As well you can download the KFC […]
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Probiotics for Histamine Intolerance | Mast Cell Disorder
Alison Vickery
Chris Kresser outlines the probiotics he recommends for histamine intolerance and mast-cell activations disorder
Digestive Care Probiotic Supplement, 28 capsules – Align : Probiotics
Jean Coutu
Get more details on Digestive Care Probiotic Supplement, 28 capsules, including product details, pricing and availability.
Three Steps to Optimal Liver Health
by Dr. Sara Celik @ Renew Life Canada
Tue Sep 20 07:16:45 PDT 2016
If you’re like me, you do your best to take care of your health. You eat well, drink adequate water, and exercise regularly. For the most part, life is pretty good. But a part of you feels it could be better. Perhaps you want to jump out of bed in the morning before your alarm Continue reading
The post Three Steps to Optimal Liver Health appeared first on Renew Life Canada.
Sudbury, Ontario
by Renew Life @ Renew Life Canada
Tue Jun 07 14:00:17 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Sudbury, Ontario appeared first on Renew Life Canada.
IBS Symptoms: 11 Things You Need To Know About Irritable Bowel Syndrome
HuffPost Canada
You’ve probably heard of IBS, but do you really know what it is? Some of the mystery and confusion around the condition comes from the fact that we don’t really know what causes it, and that symptoms...
Prince Albert, Saskatchewan
by Renew Life @ Renew Life Canada
Tue Oct 18 13:45:47 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Prince Albert, Saskatchewan appeared first on Renew Life Canada.
Probiotic Capsule Douche Taking Leaky Gut
by @ Probiotics Belaw
Sun Jan 07 17:11:46 PST 2018
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 […]
Best Probiotics For Irritable Bowel Syndrome (IBS): Explained in Plain English
DIET vs DISEASE
This article reviews the best probiotics for IBS based on current evidence... explained in a way you can understand.
Best Probiotic Strains For Constipation Tnm Classification Cancer
by @ Probiotics Belaw
Sun Jan 07 17:59:25 PST 2018
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 […]
Ellen DeGeneres Contests – Win a 65” TCL Roku TV
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 07:39:47 PST 2018
Ellen DeGeneres Contests. Win a 65” TCL Roku TV! Easy entry form to enter this contest. Rules: Single entry Open to Canada and United States Excludes Quebec Ages 18+ Click here to enter Contest from Ellen DeGeneres Contest ends on February 13, 2018 at 06:00 AM PST Tip if this contest hates your “postal Code: enter: 00000 […]
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Post lyme disease treatment advice...diet, bpc 157 and or?
by @ ImmInst Active Topics
Sun Feb 11 17:35:26 PST 2018
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
Joe Fresh Coupon Code – Save 25% off (Feb 12 Only) + Save 30% off select Sleepwear
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 09:47:40 PST 2018
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G7 Canada Coupon: Instant Coffee Savings
by Theresa @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 18:34:52 PST 2018
New G7 Coupon for Instant Coffee Save $0.75 off on G7 Instant Coffee Available in Print Format Only Print Coupon Today ( Search G7 Vietnamese Coffee) G7 Coupon Expiry Date is unknown What is G7 Instant Coffee? G7 claims to be a gourmet instant coffee! How does that work? Well its coffee taht is full […]
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Align Review | (Updated) #1 Doctor Recommended Probiotic?
DietSpotlight
Is Align an effective probiotic supplement? Evidence-based look at Align ingredients & side effects. Real customer reviews & results.
PM says time to recognize anti-black racism exists
by @ CTVNews.ca - Top Stories - Public RSS
Mon Feb 12 17:48:00 PST 2018
At a reception marking Black History Month, Justin Trudeau says it's time Canadians acknowledged that racism and unconscious bias against black people exist in this country.
Probiotic Deficiency Brands Yogurt Are What
by @ Probiotics Belaw
Sun Jan 07 20:32:45 PST 2018
Did you know that there are many ways to Cleanse the body? These include colon cleanse juice cleanse the master cleanse raw diet cleansing and fiber cleanses. Symptoms Probiotic Deficiency probiotics in prevention of antibiotic associated diarrhea meta analysis safety pregnancy Brands Yogurt Are What include: colon cleanse colon cleansing colon cleanses detox. Probiotic Deficiency […]
Align Printable Coupon - Save $3 Off Any Align Product (New) ~ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Align Coupons For Canada There is a new Align Coupon for you! Save $3.00 on any Align Probiotic Supplement (excludes trial/travel size, value/gift/bonus packs) Print your coupon Here Expiry date unknown. Available for a limited time, while quantities last. * indicates required Email: * Align Pro Biotic Align is a pro biotic supplement that …
Twinings Tea Coupon Code for Canada
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 09:11:39 PST 2018
New Twinings Tea Coupon Code for Canada. Save 10% off any Twinings Tea Product (first 100 orders) FREE Tea Samples with each order FREE Shipping This Twinings Tea Coupon Code is available online only. At Checkout, Use Coupon Promo Code TWININGS10 SHOP Twining Tea Online Here Coupon Expiry date is Unknown Find More Grocery Coupons Here. […]
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Are all probiotics created equal? A HOW TO guide on picking a probiotic for your child
Naturally Healthy Kids
The research on the good bacteria in the gut has helped us understand how to prevent and treat gut related issues. Most people take a probiotic or give one to their child when they have been on an …
Nestle Coupons: Save on Nestle Products with Printable Coupons
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 07:22:45 PST 2018
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Molson Canadian Contest – WIN a Molson Mini Fridge with Team Canada
by Theresa @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 17:11:39 PST 2018
Molson Canadian Mini Fridge Contest. Molson Sponsored – From Team Canada Olympic Team (Host of contest) Enter for a chance to WIN a Molson Mini Fridge. The approximate value of each Prize is $300.00 CAD. Easy Form to fill out! Good Luck! Rules Open to residents of Canada only Quebec Friendly Age of Majority Daily Entry […]
The post Molson Canadian Contest – WIN a Molson Mini Fridge with Team Canada appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Boushie's family meets federal ministers after acquittal in murder trial
by @ CTVNews.ca - Top Stories - Public RSS
Mon Feb 12 13:14:00 PST 2018
The grieving relatives of a First Nations man whose accused killer was acquitted by a Saskatchewan jury are meeting with federal ministers to take what they call a first step in the long road to reforming Canada's justice system.
Danone Oikos Contest: WIN Your Dream Date for Two
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 10:25:52 PST 2018
Oikos Canada Facebook Contest OIKOS® MIX YOUR VALENTINE’S DAY CONTEST Enter to WIN your dream date for two! 1 Prize consisting of gift cards to a restaurant, spa,hotel,cinema,etc..depending on what choice you make in your entry. The approximate total and maximum retail value for the prize is three hundred dollars ($300 CAD). To enter this […]
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Colorectal Cancer Vascular Invasion Shelf Australia Stable
by @ Probiotics Belaw
Sun Jan 07 12:42:11 PST 2018
Residual treatment disparities after oncology referral for rectal cancer. Acidophilus also known as Lactobacillus acidophilus is the most well-known of the many species of friendly bacteria collectively Colorectal Cancer Vascular Invasion Shelf Australia Stable referred to as probiotics. Colorectal Cancer Vascular Invasion Shelf Australia Stable marshall MD Lombardi Comprehensive Cancer Center Ligand Binding and Dimerization […]
The Best Intestinal Probiotics for IBS: Get the Germs You Need
Solving the IBS Puzzle
Research shows that b.infantis, is one of the best intestinal probiotics for IBS.
Slammers Snacks Giveaway: Win a Case of Slammers this Week
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 15:30:32 PST 2018
New Slammers Snacks Contest for 2018 Enter to win a case of Slammers this week! Simply comment on the official facebook or instagram contest post this with #iSpySlammers for a chance to win a case of Slammers! Good Luck!! Rules: Open to Residents of Canada or U.S Quebec Friendly 18 or Older Valid facebook OR instagam account Single […]
The post Slammers Snacks Giveaway: Win a Case of Slammers this Week appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Probiotics During Pregnancy
American Pregnancy Association
Thinking about using probiotics during pregnancy? If so, you may want to read this article provided by the American Pregnancy Association.
NeoStrata Giveaway: WIN Neostrata AquaYouth Filling Anti-Wrinkle Cream
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 09:05:10 PST 2018
NeoStrata Contest Enter for your chance to WIN a Neostrata AquaYouth Filling Anti-Wrinkle Cream! To participate, simply comment on the official contest post and tell your plans for Valentine’s Day for your chance to win. You can enter on facebook or instagram. Good Luck! Rules: Canada Residents Only Quebec Friendly Age of majority Single Entry per social media […]
The post NeoStrata Giveaway: WIN Neostrata AquaYouth Filling Anti-Wrinkle Cream appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
IBD Research and Treatment: Canada’s Fame and Shame
by GIS @ Gastrointestinal Society
Tue Sep 12 13:22:05 PDT 2017
Patients, Advocates and The Cameron Institute, issue call for equal access to IBD treatments CAMBRIDGE, ONTARIO (September 12, 2017) – Approximately 233,000 Canadians know how it feels to wake up every day with IBD (Inflammatory Bowel Disease), which includes Crohn’s Disease and Ulcerative Colitis – painful autoimmune disorders which attack the gastrointestinal tract.1,2 A new [...]
The post IBD Research and Treatment: Canada’s Fame and Shame appeared first on Gastrointestinal Society.
Cabela’s Deals – Winter Liquidation Sale – Save up to 50% off
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 08:29:13 PST 2018
New Cabela’s Deals for Canada 2018. Winter Liquidation Sale – Save up to 50% off Men’s Apparel Clearance Deals Save up to 60% off Women’s Apparel Clearance Deals Save up to 60% off Hunting Apparel Clearance Deals Save up to 60% off Footwear Clearance Deals Save up to 60% off All Shoreline & Propel Products […]
The post Cabela’s Deals – Winter Liquidation Sale – Save up to 50% off appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Cleansing: Just What The Doctor Ordered
by Renew Life @ Renew Life Canada
Fri Jun 03 12:57:25 PDT 2016
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Cleansing: Just What The Doctor Ordered appeared first on Renew Life Canada.
Probiotics' Benefits May Be More Than a Gut Feeling
WSJ
Probiotics, believed to help with digestion, are increasingly being studied to treat wide-ranging conditions, from colic to cholesterol and the common cold.
Natural Body Cleansing: What are the Benefits and Where to Begin?
by Renew Life Team @ Renew Life Canada
Tue Sep 13 07:40:12 PDT 2016
Each day we are confronted by harmful toxins in the air we breathe, the food and water we consume, and even in the products we use every day to make our lives more convenient. Over time, those toxins can build up in the body and impact our overall health. For this reason, many health experts Continue reading
The post Natural Body Cleansing: What are the Benefits and Where to Begin? appeared first on Renew Life Canada.
Align probiotic - April 2014
BabyCenter Canada
I'm not sure if anyone out there can answer this (or I just ask my doc the next time) but before I got pregnant I was on the probiotic 'Align' for my mild IBS signs. I stopped it at 6 weeks when I found out I was pregnant as I was not sure if it was safe. Now my symptoms are starting and I was wondering if it was safe or not.Thanks!
Knorr Lunar New Year Lucky Draw Contest: Win a $4000 Cruise & More
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 16:45:12 PST 2018
Knorr Lunar New Year Lucky Draw Enter to WIN a $4000 Cruise, $1500 Airline ticket or More One participant is eligible to win 1 Grand Prize consisting of: One $ 4000 Cruise Trip paid out in travel gift vouchers to be used towards a trip wherever the winner chooses up to the maximum amount on the voucher. […]
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Kernels Contests ~ Win a FREE Gift Card Each Monday Plus Win a Trip to Spain
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 05:30:15 PST 2018
Kernels Canada Contest. Kernels Weekly MONDAY BLITZ Contest 2018. Enter for your chance to Win a $25 Kernels Gift Card. Every Monday, check the Kernels Facebook page for the Monday Blitz Contest post. Simply comment and answer any question they may ask between 3:00-11:59pm EST, and you could be chosen as the lucky winner. Rules: Single Entry […]
The post Kernels Contests ~ Win a FREE Gift Card Each Monday Plus Win a Trip to Spain appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Winnipeg, Manitoba
by Renew Life @ Renew Life Canada
Wed Aug 31 07:46:56 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Winnipeg, Manitoba appeared first on Renew Life Canada.
GI Society Receives the BCAB Humanitarian Award
by GIS @ Gastrointestinal Society
Mon Jun 26 09:00:07 PDT 2017
British Columbians will soon be invited to get good advice about their gut at Badgut.org, thanks to a generous airtime donation by the province’s broadcasters. The British Columbia Association of Broadcasters (BCAB) announced its members have chosen the GI (Gastrointestinal) Society and its associated registered charity, the Canadian Society of Intestinal Research, as this year’s [...]
The post GI Society Receives the BCAB Humanitarian Award appeared first on Gastrointestinal Society.
Align Probiotic Review
ProbioticsGuide.com
Detailed review of Align Probiotic. See how this probiotic supplement compares against all the others!
Enteric Coated Probiotics Review - Which are the Best to Buy?
Nootriment - Health Supplement Reviews and Research
Enteric Coated Probiotics Supplements provide more live bacteria cultures (CFUs) for gut health. Best Enteric Coated Capsules to Buy Online.
Are all probiotics created equal? A HOW TO guide on picking a probiotic for your child
by Sonya @ Naturally Healthy Kids
Mon Feb 24 17:49:52 PST 2014
The research on the good bacteria in the gut has helped us understand how to prevent and treat gut related issues. Most people take a probiotic or give one to their child when they have been on an antibiotic or if there is a digestive issue. So let’s start there. Which probiotic should you take after a round […]
Old Navy Coupon Codes – Save 30% off Your Order
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 05:57:23 PST 2018
Old Navy Coupon Codes for Canada. Save 30% off Your your Order This Old Navy Coupon Code is valid Online only. To get your discount, use promo code at checkout: TREAT Old Navy Coupon Codes are valid until February 12, 2018 @ 11:59 pm ET Check here for other Old Navy deals that may be on. Old […]
The post Old Navy Coupon Codes – Save 30% off Your Order appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Pregnant? Take probiotics to prevent eczema in your baby!
by Natural Care Clinic @ Naturally Healthy Kids
Sun Feb 24 13:23:48 PST 2013
Women who take probiotic supplements during pregnancy decrease risk of eczema in their babies. http://mobile.reuters.com/article/idUSBRE89P01E20121026?irpc=932
Klaire Labs Ther-Biotic Children’s Chewable Review
by Kate Watson @ ProbioticsGuide.com
Wed Jan 10 19:43:30 PST 2018
Detailed review of Klaire Labs Ther-Biotic Children’s Chewable. See how this probiotic supplement compares against all the others!
The post Klaire Labs Ther-Biotic Children’s Chewable Review appeared first on ProbioticsGuide.com.
Trump: 'Canada does not treat us right'
by @ CTVNews.ca - Top Stories - Public RSS
Mon Feb 12 11:55:00 PST 2018
U.S. President Donald Trump is complaining about Canadian trade practices while threatening a tax on international imports, indicating Monday that the idea of some form of border fee remains alive.
Align Probiotics TV Commercial, 'Live 24/7'
iSpot.tv
A mother and daughter enjoy a day at the fair with rides, tiaras and cotton candy. The mother uses Align Probiotics for digestive health support.
Cabela’s Coupons Code ~ FREE Shipping with $99 Minimum Order
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 08:23:41 PST 2018
The Latest Cabela’s Coupons Codes. Get FREE Standard Shipping with $99 Minimum Order Coupon codes are valid online or with phone orders only. Use Promo Code: GEARUP at checkout Gift cards/e-gift cards do not apply towards order minimum. Cabela’s Coupons Offer end date is February 25, 2018 Find More Cabela’s Offers Here. * indicates required Email: […]
The post Cabela’s Coupons Code ~ FREE Shipping with $99 Minimum Order appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Post lyme disease treatment advice...diet, bpc 157 and or?
by @ Health
Sun Feb 11 17:35:26 PST 2018
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
Life Extension FLORASSIST GI Review
by Kate Watson @ ProbioticsGuide.com
Sat Nov 18 16:16:14 PST 2017
Detailed review of Life Extension FLORASSIST GI. See how this probiotic supplement compares against all the others!
The post Life Extension FLORASSIST GI Review appeared first on ProbioticsGuide.com.
2017 Survey Report: Clostridium difficile Infection
by GIS @ Gastrointestinal Society
Wed Jan 17 10:09:47 PST 2018
The GI Society represents Canadians living with gastrointestinal diseases and disorders, including those who have experienced Clostridium difficile infection (CDI), and the devastating digestive symptoms that occur from this infection. We offer patient education on a wide array of GI conditions, in text and video formats, including a video on the development, symptoms, and treatments [...]
The post 2017 Survey Report: <em>Clostridium difficile</em> Infection appeared first on Gastrointestinal Society.
What Is The Best Probiotic? Top 7 Probiotics Reviewed For 2017
The Jerusalem Post | JPost.com
Learn which probiotic can help you to lose weight, improve digestion, boost immunity, and feel your best.
Too Much Probiotic Food Stool Hard
by @ Probiotics Belaw
Sun Jan 07 13:45:13 PST 2018
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 […]
Colostrum Probiotic Prospect Between Cancer Symptoms Difference Hemorrhoids
by @ Probiotics Belaw
Sun Jan 07 20:05:01 PST 2018
Dec 1 2014 – shoppingbargains. The following links allow you to view full publications. Colostrum Probiotic Prospect Between Cancer Symptoms Difference Hemorrhoids weight loss with no known reason ; treatment of colon cancer may involve removing the tumor Contains Vitamin E Vitamin B Vitamin C Changes in cancer incidence among Japanese migrants to the United […]
Natrogix Probiotic 40 Billion Review
by Kate Watson @ ProbioticsGuide.com
Mon Dec 04 10:23:34 PST 2017
Detailed review of Natrogix Probiotic 40 Billion. See how this probiotic supplement compares against all the others!
The post Natrogix Probiotic 40 Billion Review appeared first on ProbioticsGuide.com.
Best Ultimate Flora Probiotic Adults Best For Eczema
by @ Probiotics Belaw
Sun Jan 07 21:04:22 PST 2018
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 […]
Align Jr Chewable Probiotic Supplement for Kids, Cherry, 24 Count - Walmart.com
Walmart.com
Free 2-day shipping on qualified orders over $35. Buy Align Jr Chewable Probiotic Supplement for Kids, Cherry, 24 Count at Walmart.com
Canadian who was detained by al Qaeda affiliate in Syria describes harrowing ordeal
by @ CTVNews.ca - Top Stories - Public RSS
Mon Feb 12 17:40:51 PST 2018
Chatham, Ont., man Sean Moore is speaking out for the first time about the torture he experienced at the hands of an al Qaeda affiliate in Syria.
Probiotics Yogurt For Ibs Intolerance Milk Lactose
by @ Probiotics Belaw
Sun Jan 07 17:33:47 PST 2018
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 […]
A&W Coupons ~ Print or Show on a Mobile Device
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 05:50:02 PST 2018
A&W Coupons for Canada Print and redeem these A&W coupons (or show them from your Smartphone) to save big on your next visit to A&W restaurants. FREE 3 Stack of Pancakes with the purchase of a stack of 3 pancakes at regular price FREE Fries with purchase of a Teen Burger at regular price FREE […]
The post A&W Coupons ~ Print or Show on a Mobile Device appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
No Sugar Probiotic Yogurt Fat Stomach
by @ Probiotics Belaw
Sun Jan 07 14:17:16 PST 2018
Ingredients: Viable yogurt starter culture of nonfat milk solids and whey containing Lactobacillus bulgaricus (LB-51) and Strepococcus thermophilus bacteria (in precise Bulgarian proportions). No Sugar Probiotic Yogurt Fat Stomach help with gas and bloating. His tumor the size of a baseball was already starting to strangle the portal vein going into the liver. Activia Parfait […]
Well.ca Contest: WIN a beautiful Amped & Co LED Heart Wall Light
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
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Cryonics
by @ Articles - Articles
Tue Feb 21 13:06:47 PST 2012
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
- Existing Cryonics Organizations
- Cryonics Services Offered
- Sizes of the Organizations
- Whole Body/Neuro Options
- Cryopreservation and Yearly Fees
- Human Cryopreservation Procedures
- Funding Cryonics by Insurance
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.
| NAME | LOCATION | INCORPORATED | NON-PROFIT ? |
|---|---|---|---|
| Alcor Life Extension Foundation | Scottsdale, Arizona | 1972 | Yes |
| American Cryonics Society (ACS) | Cupertino, California | 1969 | Yes |
| Cryonics Institute (CI) | Clinton Township, Michigan | 1976 | Yes |
| KrioRus | Moscow, Russia | 2005 | No |
| Oregon Cryonics | Salem, Oregon | 2005* | No |
| Suspended Animation, Inc (SA) | Boynton Beach, Florida | 2002 | No |
| Trans Time, Inc. | San Leandro, California | 1972 | No |
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).
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.
| NAME | PATIENT ADMINISTRATION | PERFUSION | STORAGE | SST |
|---|---|---|---|---|
| Alcor | Yes | Yes | Yes | Yes |
| ACS | Yes | Yes* | No* | Yes* |
| CI | Yes | Yes | Yes | No* |
| KrioRus | Yes | Yes | Yes | No |
| Oregon Cryonics | Yes | Yes | Yes | No |
| SA | No* | No | No | Yes |
| Trans Time | Yes | No | Yes | No |
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.
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.
| NAME | MEMBERS | FUNDED MEMBERS | PATIENTS | STAFF |
|---|---|---|---|---|
| Alcor | 1,639* | 1,132* | 150 | 9* |
| ACS | ?* | ?* | 20* | 1* |
| CI | 1,384* | ?* | 151* | 3* |
| KrioRus | N/A | N/A | 52 | 7* |
| Oregon Cryonics | 8* | N/A | 6 | 5* |
| SA | N/A | N/A | N/A | 3* |
| Trans Time | ? | ? | 3 | 1? |
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
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.
| NAME | WHOLE BODY | NEURO |
|---|---|---|
| Alcor | Yes | Yes |
| ACS | Yes | No* |
| CI | Yes | No |
| KrioRus | Yes | Yes |
| Oregon Cryonics | No | Yes |
| SA | N/A | N/A |
| Trans Time | Yes | Yes |
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.
| NAME | WHOLE BODY | NEURO | YEARLY FEES |
|---|---|---|---|
| Alcor | $200,000* | $80,000* | $620* |
| ACS | $155,000* | N/A | $376* |
| CI | $28,000* | N/A | $120* |
| KrioRus | $36,000* | $12,000 | None |
| Oregon Cryonics | N/A | $25,000* | None |
| SA | N/A | N/A | None |
| Trans Time | $150,000 | $50,000 | $96* |
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.)
A Gastroenterologist’s Guide to Probiotics
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The enteric microbiota contributes to gastrointestinal health and its disruption has been associated with many disease states. Some patients consume probiotic products in attempts to manipulate the intestinal microbiota for health benefit. It is important ...
Probiotics Make Vaccines More Effective (And May Replace Them!)
by Lisa Richards @ The Candida Diet
Wed Feb 07 15:24:07 PST 2018
As most of us know, probiotics are a great way to improve gut health. Many scientific studies have shown that taking probiotic supplements or eating fermented foods can lead to better digestion, healthy elimination, and a stronger immune system. These benefits are crucial to the daily maintenance of the body and its many functions. Your […]
The post Probiotics Make Vaccines More Effective (And May Replace Them!) appeared first on The Candida Diet.
How To Easily Make Your Own Probiotic-Rich Sauerkraut
by Kate Watson @ ProbioticsGuide.com
Tue Jan 16 21:12:18 PST 2018
If you’ve been looking for homemade recipes for fermented foods, I hope you enjoy this one! Let’s look at an easy, probiotic-rich sauerkraut recipe.
The post How To Easily Make Your Own Probiotic-Rich Sauerkraut appeared first on ProbioticsGuide.com.
Nootropics in human trials (Intro)
by @ Articles - Articles
Sat Sep 09 06:57:38 PDT 2017
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. |
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.
Using Probiotics for Healthy Traveling - The Healthy Home Economist
The Healthy Home Economist
Most illness during travel including nasty intestinal bugs can be avoided with probiotics with a regimen that should start two weeks before you leave.
Alimentary Health Launches New Precision Probiotic in Ireland - APC Microbiome Institute | University College Cork
APC Microbiome Institute
Linking Irish science with industry and society through excellence in research, education and outreach in gastrointestinal health.
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Fight Aging! Newsletter, February 12th 2018
by @ LongeCityNews
Sun Feb 11 01:51:59 PST 2018
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
Flamingo Chicken Coupons – Save $1.00 Print Today
by Theresa @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 18:16:07 PST 2018
New Flamingo Coupon ( Printable) Canada New Save $1.00 off any breaded Flamingo chicken product Available in Print Format Only. Click Here to Print Coupon Flamingo Coupon Expires on March 12, 2018 Has this Expired? Then Check out other Grocery Coupons * indicates required Email: * Flamingo Products: Flamingo has various products here’s a small […]
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Probiotics for Irritable Bowel Syndrome | Gastrointestinal Society
Gastrointestinal Society
In this article, we will review evidence for the use of probiotics in the treatment of irritable bowel syndrome (IBS) in adults. However, this does not replace the advice of your physician, whom you should always consult with for specific treatment recommendations. The World Health Organization defines probiotics as “live microorganisms which when administered in …
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...
What are the Best Probiotics for IBS? - Gutsify
Gutsify
Gas, bloating and cramps got you down? The best - and easiest - thing you can do for your gut is to add one of the best probiotics for IBS to your daily diet.
Probiotics And Weight Gain Cake Chocolate Sauerkraut
by @ Probiotics Belaw
Sun Jan 07 13:11:32 PST 2018
If you are taking any prescription medications you should talk to your doctor first before using TruBiotics. Probiotics And Weight Gain Cake Chocolate Sauerkraut click here to read about Just 4 Kids! Potent Probiotics with Organic Prebiotics Powder. Do All Yogurt Have Probiotics They certainly do when they’re made Even though probiotics are needed to […]
Align: The Probiotic Supplement w/ Bifantis, a Special B. infantis
PowerOfProbiotics.com
Align is the only probiotic supplement with Bifantis, a strain of Bifidobacterium infantis, that shows benefit for issues related to the colon. Is it the probiotic supplement for you?
Sault Ste Marie, Ontario
by Renew Life @ Renew Life Canada
Tue Jun 07 14:13:38 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Sault Ste Marie, Ontario appeared first on Renew Life Canada.
Purina Canada ~ Cat and Dog Food Printable Coupons
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 07:48:32 PST 2018
Purina Coupons for Cat Chow Save $3.00 on one (1) bag of Purina Cat Chow Available in Print format only. Maximum 2 prints per household. While quantities last Get Purina Cat Chow Coupon Here (via hidden smartsource) Purina Coupons Expiry is unknown **Scroll down to see all the other Purina Coupons Purina Coupons for Dog Chow Save $4.00 on one […]
The post Purina Canada ~ Cat and Dog Food Printable Coupons appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Charlottetown, Prince Edward Island
by Renew Life @ Renew Life Canada
Tue Jul 05 17:41:27 PDT 2016
Cleansing: Just What The Doctor Ordered
Dr. Sara Celik shares simple strategies that she has used to transform the health of thousands of Canadians.
The post Charlottetown, Prince Edward Island appeared first on Renew Life Canada.
What Are Prebiotics And Do You Need Them?
by Kate Watson @ ProbioticsGuide.com
Fri Dec 08 13:17:00 PST 2017
Are you wondering what prebiotics are and what they have to do with your health? Find out now if they’re a total waste of money or a digestive necessity…
The post What Are Prebiotics And Do You Need Them? appeared first on ProbioticsGuide.com.
Saccharomyces Boulardii
by Julia @ Consumer's Health Report
Thu Feb 08 14:02:28 PST 2018
Saccharomyces Boulardii What is Saccharomyces Boulardii Saccharomyces boulardii is a type of yeast that is tropical. Harvested from a lychee and mangosteen fruit in 1923. is sometimes used as a probiotic, and can be found in probiotic supplement, with the...
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Scotiabank Charity Challenge
by GIS @ Gastrointestinal Society
Thu Apr 13 12:11:27 PDT 2017
The Gastrointestinal Society is thrilled to announce that it will be participating in the 2017 Scotiabank Charity Challenge! The Vancouver races will be happening on June 25, 2017, and the GI Society needs YOUR help to raise funds and awareness for those living with gastrointestinal and liver conditions across Canada. Runners can participate in either [...]
The post Scotiabank Charity Challenge appeared first on Gastrointestinal Society.
Breakthrough Research Finds CFS is An Immune Condition
by Alison Vickery @ Alison Vickery
Mon May 01 00:00:25 PDT 2017
Alison Vickery
Alison Vickery - The Low Histamine Coach
Australian scientists have linked chronic fatigue syndrome (CFS) to a genetic defect in immune cell receptors putting to rest once and for all the pathology of this much-maligned condition. The research undertaken by the National Centre for Neuroimmunology and Emerging Diseases (Griffiths University) found that an inherited genetic defect means that cells do not work optimally. […]
Breakthrough Research Finds CFS is An Immune Condition
Alison Vickery
Michelina’s Coupon – Save $1.00 on ANY 6 Products
by Andria @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 07:28:13 PST 2018
Michelina’s Coupon for Canada. Save $1.00 on the purchase of ANY 6 Michelina’s Products Michelina’s Coupon is available in Print Format Only PRINT Coupon HERE via Michelina Coupon Expiry date is unknown. Pasta Savings Expired? Try out other Grocery Coupons * indicates required Email: * Michelina’s Canada Frozen dinners that are quick, easy, and […]
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Pb8 Probiotic Canada Burping
by @ Probiotics Belaw
Sun Jan 07 16:13:41 PST 2018
Hens’ eggs are the type of egg most When there is a need to give high doses of chemotherapy to a specific area of the body it may be given by a regional method. Virtual Reality Laparoscopic Sigmoid Colectomy Virtual reality colorectal surgery is demonstrated here by medial to lateral mobilisation of the sigmoid colon […]
SmartyPants Adult Probiotic Complete Review
by Kate Watson @ ProbioticsGuide.com
Thu Feb 08 21:12:24 PST 2018
Detailed review of SmartyPants Adult Probiotic Complete. See how this probiotic supplement compares against all the others!
The post SmartyPants Adult Probiotic Complete Review appeared first on ProbioticsGuide.com.
When Should I Take a Probiotic If I’m on Antibiotics?
by Linda Agin @ Bottom Line Inc
Mon Feb 12 03:16:44 PST 2018
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.
Apply for FREE La Roche-Posay Toleriane Sensitive Hydrating Care facial moisturizer -Go!
by Karla @ Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com
Mon Feb 12 11:10:58 PST 2018
New Chickadvisor and La Roche Posay Free Product Review Offer It’s a fabulous new offer from La Roche-Posay featuring their brand-new Toleriane Sensitive Hydrating Care facial moisturizer! 250 Canadian women will be among the first in Canada to try this product specifically designed to offer soothing 48-hour hydration and immediately comfort skin and reduce sensitivity. Apply at the […]
The post Apply for FREE La Roche-Posay Toleriane Sensitive Hydrating Care facial moisturizer -Go! appeared first on Canadian Freebies, Coupons, Sweepstakes Deals~ Canadianfreestuff.com.
Children’s Health Fair
by Natural Care Clinic @ Naturally Healthy Kids
Mon Nov 22 15:21:42 PST 2010
Join us for the 2nd Annual Children’s Health Fair at the Burlington Art Centre on May 14th from 10 am – 4 pm. Exhibitors include: Autism Halton http://sites.google.com/site/autismhalton/Home Ontario HBOT www.ontariohbot.com Rainbow Connections – RDI www.rainbowconnections.com Burlington Aligned Chiropractic| www.burlingtonchiropractor.ca Lucie Stephens Food Coach Voila Gluten Free Bakeree http://www.voilaglutenfreebakeree.com Toys, Tools and Treasures www.toystoolsandtreasures.com […]
Why do some turtles outlive humans?
by @ Articles
Wed Feb 08 16:45:06 PST 2017
(⇒ 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
Probiotic Yogurt On Skin Oz Usana Dr
by @ Probiotics Belaw
Sun Jan 07 19:23:53 PST 2018
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 […]