Life Extension Supplements: A Reality Check

In a paper published late last year, a cautious and expert biochemist reports that none of the most popular “life extension supplement” mixes actually extend life span in mice.


Stephen Spindler, biochemistry prof at UC Riverside, has been warning us for years that supplements, herbal extracts and nutraceuticals are, on the whole, ineffective for healthy adults, and that some may actually shorten life expectancy.  Spindler’s lab has done many life extension studies on mice (summary), almost always with negative results.  One recent report included separate life span tests on extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, curcumin, morin, pycnogenol, quercetin, and taxifolin.

One of the themes in his papers is that caloric restriction is the only thing that works consistently, and that many of the treatments that seem to offer life extension are subtley inducing caloric restriction, (and this goes unreported by the investigators).  But there are so many substances to test, and each lifespan test in mice is so expensive, that Spindler has suggested gene expression profiles as a shortcut to identifying candidates for further testing.

Another approach is to test many substances at once in a mouse life extension cocktail.  Another rationale for this kind of testing is that we know that natural fruits and vegetables contribute to a long and healthy life, so perhaps it takes a complex combination of nutrients to be effective.  Late last year, Spindler reported on his experiments, feeding commercial “life extension” mixes to hybrid mice.  The results are a bracing cold shower for those of us who take a variety of carefully-chosen supplements each day – and a personal caution to me, since I have recommended supplements on my Aging Advice web page.  [Link to Spindler combinations paper]



Seven of the eight graphs of survival time in the paper look like this.


The mice that ate the supplements and the mice that ate ordinary mouse chow had exactly the same pattern of mortality.

(The agreement between treatment and control is so perfect that, if it were a scientist of less integrity, I would suspect the data had been doctored.  But in Spindler’s case, I think the consistency of the results bears witness to his expertise in all aspects of mouse husbandry and experimental desgin.  Clearly, his lab has benefited from a lot of experience, and has adopted methods of caging, feeding, watering, temperature and light control that eliminate a lot of the usual experimental scatter.  Even choice of the mouse strain was subject to thoughtful analysis.)

The eighth treatment group showed slightly shorted life span.



Our results do not support the hypothesis that simple or complex combinations of nutraceuticals, including antioxidants, are effective in delaying the onset or progress of the major causes of death in mice. The results are consistent with epidemiological studies suggesting that dietary supplements are not beneficial and even may be harmful for otherwise healthy individuals. [Spindler]


What substances were tested?

There were eight test groups with different mixtures of supplements, one control group fed only standard mouse chow, and one calorically restricted “positive control” that got less mouse chow (and lived longer).  There was some overlap among mixtures of compounds in the eight test groups.  The list of substances included is long.  Here are highlights:


Alpha Lipoic Acid
Blueberry extract
CoQ10 (ubiquinol)
Green tea
Many minerals
N-Acetyl Cysteine
Pomegranate extract
Silymarin (milk thistle)
Vitamin A complex
Various B vitamins
Vitamin C
Vitamin D3
Vitamin E
Vitamin K2

Two of these substances (metformin and melatonin) have a credible history of life extension potential in past experiments with mice.  Spindler doesn’t comment, and I leave this as an open question.  There is credible data in humans for two more (vitamin D and aspirin), both of which have been shown to lower all-cause mortality.  I am not aware of rodent life span studies of vitamin D or aspirin, but I trust that one of you, my readers, will point me to a reference.

Notably absent were prescription drugs that have been shown to lengthen mouse life span in the past: deprenyl, metformin, and rapamycin.  The first two are, in my opinion, suitable for general human use.


Fish oil responsible for shortened life span

Why did experiment #8 actually shorten life span (by about 9%)?  Spindler speculates that it might be due to the way mice respond to omega 3 fatty acids (fish oil).  He cites not-yet published data in which fish oil alone was found to shorten life span.  Another possibility he mentions is the well-established fact that plant compounds can mimic the effects of mammalian hormones, and that indiscriminate overdoses of plant extracts can throw the metabolism into dysregulation.


Caveats: Mice are not humans

Some things about aging metabolism in mice are the same as humans, and some are different.  One principal difference is that aging mice die predominantly of cancer, while aging humans die of cardiovascular disease, cancer, and Alzheimer’s disease.  Aging mice, like aging humans, are flooded with hormones that dial up inflammation that destroys healthy tissue and heightens risk of cancer [ref].  So the failure of anti-inflammatory ingredients (e.g. omega-3 fats, aspirin) in these mixes to have a life extension effect is particularly puzzling.  Unlike humans, aging mice do not suffer from short telomeres, so we might hope that telomerase activators (e.g. silymarin, astragalus extracts, ashwagandha, bacopa) would benefit human life span even if they do not help mice.

A partial explanation for the null results is that some of the combinations include anti-oxidant vitamins, which have been shown generally to shorten lifespan.  This could be counteracting the benefits of some ingredients that might provide benefits on their own.  Likewise for the fish oil that was included in one of the ineffective combinations.


What does this leave us?

There is epidemiological evidence for mortality reduction in humans from small doses of NSAIDs (ibuprofen, aspirin) and for large doses of vitamin D.

There is evidence from rodent experiments that melatonin, metformin and deprenyl extend life span.  There are reports from one lab in Russia that SkQ should be added to this list, but it is not yet commercially available.

There is anecdotal evidence and theoretical support for telomerase activators:  astragalosides, silymarin, other herbs, carnosine, etc.  We expect these might work better in humans than in mice, though evidence is yet thin.

Everything else is speculative, and many anti-aging supplements will help some people but not others.  There is also the disturbing potential for actual harm, as Spindler emphasizes.  None of us wants to think that the mix of supplements we take might be shaving years off our life expectancies.

A one-man experiment in radical anti-aging

One reason that there is still so much uncertainty in anti-aging medicine is that we can’t do experiments on humans the way we do on mice.  So we are grateful for a few human guinea pigs who put their own bodies on the line as early adopters.  There is the Caloric Restriction Society, people who are losing weight in the hope of gaining years.  There is an on-line community of people experimenting with Buckyballs in olive oil (this may sound like a joke if you haven’t read about it before).

And then there is Jim Green of Wichita, KS.  Since 2007, Jim has been pursuing experimental strategies and claims to have set his body clock back by 15 to 20 years already.  The core of his program is telomerase activation herbs, particularly astragalus, taken in much larger quantities than the label recommends.  Jim has quite a story to tell, and this week I have interviewed him, an exclusive for ScienceBlog.

(You can read more about Jim’s career here and his anti-aging program here.)

Jim Green in 2007

Jim Green in 2013

What gave you the idea that growing younger was possible?

According to the telomere position effect data I saw early on back in 2007, telomere length impacts youthful gene expression, and gene expression is more youthful the longer the telomeres are. Furthermore, since 1998 it has been realized that senescent cells can often be restored to the youthful phenotype by transfecting them with a virus that improves hTERT transcription and boosts levels of telomerasee in the cell. In 1998, Michael Fossel published an article on this in the Journal of Anti-Aging Medicine (now Rejuvenation Research). [Another Fossel article -JJM] So there were definite grounds for optimism that lengthening telomeres with telomerase could result in rejuvenation transformations.

On the other hand, as telomeres got shorter, patterns of gene expression became more elderly and the likelihood of the onset of diseases of old age increased, according to many scientific studies. For instance, microglial cells in the brain that clean up amyloid beta plaque leading toAlzheimer’s disease fail when they become senescent. If senescence in the microglial cells (derived from hematopoietic stem cells) could be prevented, then Alzheimer’s disease due to the onset of senility might also be prevented. Similarly, when the lining of the vascular endothelium becomes senescent, it becomes more adhesive to monocytes and more likely to develop atherosclerotic plaque leading to attacks or strokes.  So taking small molecule telomerase activators effective at increasing the telomere length of components of the blood was a very good bet for effective life extension. Similarly, when dermal fibroblasts go senescent, they begin to attack the extracellular matrix, producing wrinkles. This does not happen at once to all of the fibroblasts, but gradually in a way that produces more and more defects in the extracellular matrix behind wrinkles. Thus a telomerase activator effective on dermal fibroblasts should prevent observable signs of old age such as wrinkles.


When did you start your program?  What was your program in the beginning?

I started taking telomerase activators on May 1, 2007, after reading material on TA-65 from TA Sciences.  I also had an exchange with Greta Blackburn of TA Sciences in which she emailed me promising results obtained by using TA-41, an astragalus extract which they believed would be similar in effect to TA-65.

At first I expected to be able to set back my telomere clock by up to 8 or 9 years per year, but subsequently revised this to about 5.1 years per year.

The astragalus extract actually finally turned out to work rather better, in fact, than TA-65.

I was also reading Life Extension Magazine since 2004, so I was familiar with supplements recommended by LEF to prevent diseases of old age, such as acetyl L-carnitine with alpha lipoic acid for mitochondria, L-arginine as a nitric oxide booster for rejuvenating the vascular endothelium, anticancer supplements such as garlic and ginger and turmeric, and so forth.

At first I took astragalus extracts such a Solaray Astragalus Extract, and tried GAIA Herbs astragalus extracts.  Later, I got the idea of using colostrum skin creams for telomerase activation. However I seem to have used astragalus extracts both orally and on my skin in the beginning.  This was done for two weeks before switching to a telomerase-inhibiting anticancer phase of treatment for the next two weeks, when I took medicine like curcumin, which is anticancer. If my telomerase activators tended at all to encourage cancer, I was going to squelch that every monthZin November 2009 I presented a short description of my program here For 2 1/2 years, I had relied primarily on astragalus extract for telomerase activation. However, I also got 5 grams of arginine per day to improve my nitric oxide levels and improve the length of endothelial progenitor cell telomeres.  By June of 2009 I concluded after studies of Vida Institute literature that 33 grams/day of astragalus root would serve as well or better than the 5 mg/day of astragalosides from astragalus extract that I computed I was taking. So I switched from pure astragalus extract like TA-41, which worked fine according to Greta Blackburn at TA Sciences, to astragalus root in capsules from NOW FOODS. However, I was still applying astragalus extract directly to my scalp.

[Editor’s note: Astragalus is a woody root which can be found in Chinese groceries for about $10/lb.  Traditional use would be to boil strips of astraglus to make a tea. -JJM]

What is your supplements regimen at present?  Is it still evolving?

I have posted a short summary of my present program and photo news here. It is still evolving, and by now I have 173 items at least on my list of telomerase activators that I am exploring. The numbers of the activators chronicle the order in which I found them in the literature, or were tipped off to them by other investigators, except for sub-items, which I have sometimes found more frequently.

I have continued a four-week cycle featuring telomerase activators for two weeks followed by anticancer telomerase inhibitors for two weeks.  I do things that permit cells to recover from the senescent state that are a little unusual now: I use folic acid in my colostrum solution with an amphipathic alcohol to improve absorption (rubbing alcohol = isopropyl alcohol). [Isopropyl alcohol is moderately toxic. – JJM]  I take carrots and exercise to inhibit P16INK4A, which can stop senescent cell recovery.

I have many ideas about medicine I would like to include, such as tocotrienol-rich fraction. [These are chemical cousins of vitamin E derived from grains -JJM]  For bodybuilding, I take whey protein and creatine monohydrate, although I am not attempting a championship program. I can more easily resemble a gymnast.

Besides supplements, what are you doing to stay young?

Exercise improves circulation in the brain, elevates nitric oxide levels that dialate vessels, and provides numerous growth factor telomerase activators that can be separately enhanced by various nutraceuticals. So I work out with weights, about 6 sets per muscle, using a split routine that takes 3 or 4 days.  This might be dangerous to a person with too much atherosclerotic plaque, or someone with glycation stiffening in the veinous system from high levels of sugar from ice cream. However, it tends to lower triglycerides and improve the lipid profile, and also to improve confidence and mood.

I take a slice of Swiss cheese often to get a higher vitamin K2 level to avoid calcification of the arterial system and aortic stenosis.

In what ways do you feel younger than 7 years ago?

May 2007 was my starting date, and we are now approaching May 2014.  I would say that my confidence has improved that we can finally master aging, although there is still a fair amount of suspense involved.  My physical condition oscillates somewhat, and is subject to minor perturbations. I work to get leaner in the Spring, like most people, and my self-image improves then. I look better in photographs, although I invariably puff up a bit in the Winter. In the Summer I can do pull-ups on outside chinning bars, and I get more V-shaped.     In general, I seem to look somewhat better to myself in photographs an I did 7 years ago. Last Summer I did 130 pushups, which was    an all-time record for me. I am hoping that it will go back up to that this summer.

I notice you pay attention to appearance as well as health.  Do you think there’s a connection between anti-aging skin treatments and longevity?  Or a psychological effect whereby looking younger helps you to feel younger and programs your mind to live longer?

I could dress better to improve my appearance, but my funds vanish into supplements.  Wrinkles are definitely symptomatic of the formation of senescent cells which begin to excrete factors that attack the extracellular matrix and weaken it. A weaker extracellular matrix leads to more than cosmetic problems, eventually, and less resistance available to UV radiation from the sun.  So keeping the skin healthy and young is very important for survival as well as for image. Skin cancer kills. Thin skin and failing veil cells around veins can produce bleeding, finally, perhaps even dangerous internal bleeding.

Of course, looking younger creates a sense of optimism about what may be possible, and helps reinforce a positive attitude.

What evidence do you have that your body is really younger?

Unfortunately, I was unable to do measurements of my blood component telomere lengths because of funds could not be mobilized in time. Therefore, about all I have is my collection of photographs online. There are many measures of aging and senescence that may be applied to the problem of measuring the effect when funds are available.  See .


* I wish I could say, “Testing experimental drugs on unsuspecting humans is off the table, out of the question, never done.”  The truth is that it is not as exceptional as we might wish.  And the institutions that resort to surreptitious experimentation are usually up to no good. [MK-Ultra, Nazis, antibiotics to children, Tuskegee syphilis experiments]

Mitigating risk of Alzheimer’s Disease: More important than we thought

Recent re-analysis suggests that Alzheimer’s Disease ought to be ranked with cancer and heart disease as one of the most important mortality risks for older Americans.  Some of this risk is under our control.

In a study published last week, Bryan James and colleagues at Rush Univ. Medical Center in Chicago tell us that Alzheimer’s Disease has been greatly under-reported as a cause of death.  According to current statistics, cancer and heart disease are tied for the top spot, each contributing almost ¼ of all deaths in the US.  The new study says that AD should be right up there with heart disease and cancer, accounting for about ⅕ of US deaths.  If they are right, then these Big 3 diseases of old age together account for 70% of all deaths – not just deaths among the elderly.

Previously, AD had been listed as number 6 by the US Center for Disease Control, and the new study would move AD up to the #3 spot, which had previously been claimed by emphysema.  Emphysema is way behind cancer and heart disease, and predominantly affects smokers.  It’s almost certainly true that AD has been under-reported, and it wouldn’t take very much to move it up to #3; but whether AD really accounts for a 20% risk factor overall is less clear.  Let’s take a look at their methodology.  (or if you like you can skip ahead: What can you do about your AD risk?)

What’s wrong with this study?

The methodology of the study was straightforward.  For eight years, they tracked a group of about 2500 seniors, average age 78.  They learned if each person was diagnosed with AD, and if he died.  People diagnosed with AD had on average less than 4 years to live.  The mortality rate for people diagnosed with AD under age 85 was 4.3 times higher than otherwise (and 2.8 times higher if over 85).  These numbers (4.3 or 2.8) are called “hazzard ratios”, and as it turns out, they are an easy statistic to work with, and translate straightforwardly into inferences about the mortality risk of a diagnosis of AD.

The authors make the leap that this many deaths were attributable to AD, whether AD was listed as the cause of death or not.  Is this justified?  Think about it.  They are assuming that AD is the underlying cause and (for example) heart disease might be listed as the cause of death, but the heart disease was caused by an earlier diagnosis of AD.  But isn’t it just as likely to be the other way around?  People in danger of a heart attack may undergo bypass surgery, as a result of which the brain is deprived of oxygen during surgery and cognitive impairment results.

Or maybe there are underlying conditions (e.g., high inflammation, metabolic syndrome) that put the patient at higher risk for both AD and cancer, and then the patient dies of cancer.  It’s not right to assume that AD caused the cancer, or that this patient really died of AD.

So the authors’ conclusion that AD causes half a million deaths in the US every year is certainly overstated.  Nevertheless, they’ve got a point, and AD almost certainly should be moved up to the #3 slot, especially for non-smokers.  I believe there’s a lot of truth in the idea that mortality from AD is under-reported because the proximate cause of death is frequently something else.  If nothing else, depression and institutionalization frequently follow from dementia, and both are major mortality risk factors, under many guises.  Also, I believe in an “aging clock”: regulation of the rate of aging that derives from hormones secreted in the brain.  It is not hard for me to believe that deterioration of the brain has a direct effect on aging, and through aging on other aspects of health.


Blood test predicts AD

Also reported this week was a blood test that can predict (10 false positives out of 100) who will develop AD in the ensuing three years.  The work was reported in Nature Medicine by Howard Federoff of Georgetown University.  Does the test offer a clue about the etiology of AD?  Not at all.  The test was developed using formal statistical methods.  They made lipid blood profiles for several hundred people over the age of 70, testing the specific types of fats present in the blood plasma.  Then they waited three years to see which of the people might be diagnosed with AD.  Then, after the fact, they went back and used a blind, brute-force computer search to test millions of combinations of different features in the lipid profiles to look for ways in which the people who developed AD might be consistently different from the people who didn’t.  They then tested the test, applying it to a completely different group of people to see if the same test would work to predict AD for them.  It did.

There is no biology in this approach; only mathematics, and authors of the paper do not try to parse the significance of their results.


What causes AD?

Medical science is not in agreement about the cause of AD, and it may be that the symptoms of cognitive impairment come from several causes, separately and together.  Up until a few years ago, there was a theory about amyloid plaques in the brain, tiny accumulations of misfolded proteins that the body has failed to recycle.  But that theory has faded in popularity with evidence that the plaques may be an effect rather than cause of AD.


Apoptosis of otherwise healthy neurons?  or  is it
Amyloid plaques triggering an inflammatory attack on the brain?

Everyone agrees that the proximate cause of dementia symptoms is the loss of nerve cells in the brain.  Curiously, it seems that healthy neurons may be “committing suicide”, eliminating themselves via apoptosis [ Ref1 , Ref2 , Ref3 ].  For people of my school, this is yet one more instance of the body’s suicide program, the finite life span that has been programmed into our genes by natural selection for the purpose of leveling the death rate and stabilizing ecosystems.  People who believe that aging is not programmed tell the story in terms of the amyloid plaques triggering an immune response, and it is the inflammation that leads to apoptosis.  In any case, we all agree that inflammation is a risk factor for AD, and that anti-inflammatory supplements and drugs can lower the risk of AD.  (Anti-inflammatories also offer protection against cancer and heart disease.)


What can you do control your risk of AD?

The usual stuff.  Weight control, exercise, and most everything else you do to extend life expectancy lowers risk of AD along the way.  Remaining mentally active, learning new skills, putting yourself in new situations and taking on new challenges – these are ways to keep ourselves alive and aware, and they also reduce risk of AD

Anti-inflammatories are especially helpful.  Curcumin (turmeric) is an herbal anti-inflammatory that deserves special mention because of the many studies finding a protective effect in test tubes, mice, and humans.  In India, dementia is only ¼ as common as in Europe and America, possibly because of turmeric in the diet.  There is evidence to recommend fish oil, and also studies in which fish oil does not work.  Daily, low-dose ibuprofen lowers the risk of AD, and there are mixed reports of whether aspirin does as well.

A great number of traditional herbs have been shown to be neuroprotective.  This review of neuroprotective herbs mentions Ashwaghanda, Bacopa, Carnitine, Melatonin, CoQ10, Garlic, Vitamin D, Ginseng, and Ginkgo biloba. Here is another review of herbs that might be useful for AD.  None of these is a cure for AD, but there is some clinical evidence for benefit from each.  Readers familiar with my AgingAdvice page know that I like melatonin and vitamin D for other reasons as well.

Blueberries and perhaps other berries are protective.  A substance called fisetin (chemical cousin of quercetin) found in fruits and berries may be partly responsible.  Soy products contain phytoestrogens – chemicals which resemble female hormones.  Twenty years back, it was noticed that east Asians who moved to America and adopted an American diet had lower risk of AD, and it was hypothesized that phytoestrogens from soy might increase risk of AD.  But more recently several studies seem to point in the opposite direction, that soy might protect against AD [ Ref1 , Ref2 , Ref3 ].

I’ve reported (here and here) that since November I’ve been taking deprenyl (~1mg daily) and I find that it’s making me happy and increasing my energy, much to my consternation since I’m constitutionally anti-anti-depressant.  Deprenyl (sold as Selegiline or Emsam) is neuroprotective and it’s on the short list of drugs that consistently augment the life span of rodents in the lab.


And what is the payoff for avoiding AD?

According to the new hypothesis of James, 20% of mortality risk at all ages comes directly or indirectly from dementia.  Based on a 20% reduction in mortality, I calculate (using CDC life tables for 2010) that if we can greatly reduce risk of AD with all the above measures, starting (for example) at age 50, we might add 2½ years to life expectancy.


A horrible way to die, for some

The stereotypical AD patient is depressed and isolated by failure of his memory and inability to communicate.  And sadly, this is the norm as patients become disoriented and frustrated with inability to function.  But some AD patients become happy and grateful, detached from the worries that tied them down, occasionally euphoric.


Who will I be after I die?  Who was I before I was born?

We think of life and death like 1 and 0, like on and off, without a gray zone.  But it took time for our physical selves to develop, and our brains to connect up in ways that support the conception of a separate self.  In AD, the self takes about the same amount of time to disintegrate as it took to form.

Most of us have no memories before we were three.  Perhaps it takes three years for the brain to organize itself around time and events, inner self and outer world.  All that individuation that happened during the “terrible twos” is no longer part of our remembered life.  All that bewilderment, the wonder and constant questioning, a state of deep becoming.

I think of AD as the mirror image of the child’s individuation, the gradual dissolution of self.  For many of us, that prospect is terrifying, but remember that the infant also found it terrifying to become a separate self.  If there’s any benefit we can hope to derive from a lifetime of accumulated wisdom, let it be the ability to know fear for what it is: merely a genetic program, evolved to protect the individual genome and improve our chances of passing

A Well-known Anti-aging Supplement

Carnosine is a good supplement, with many studies offering indirect evidence for effects that ought to be beneficial.  Carnosine reduces glycation (“AGE’s”) that gum up the cellular works.  Best of all, carnosine is a telomerase promoter.  But in practice, will it help us live longer?

(One of the most embarrassing blunders that a classical musician can make is to say “Schubert” when we mean “Schumann”. I been there. For someone who claims authority in the health supplements field, the corresponding gaffe is to confuse carnosine with carnitine. I done that, too.)

Carnosine is a micro-protein. Proteins are chain molecules, and they are the workhorses of the body’s metabolism, transmitting signals, transducing signals in a form of computation, and actually doing a lot of the motor work of muscles and the electrical work of nerves. These proteins are specialized to their tasks with hundreds or thousands of links to the chain. Each link is an amino acid molecule, chosen from an alphabet of 20. Carnosine is a protein with just two amino acids, named alanine and histidine. Hence, a micro-protein.

Our cells, especially muscle cells, contain significant quantities of carnosine, and young people have a lot more in their muscles than old people.  That’s a good sign.  But this same article warns that carnosine taken as a pill doesn’t find its way to the muscle cells.

Red meat contains significant amounts of carnosine. A quarter pound of beef gives you roughly as much carnosine as a 500mg capsule.

In experiments with rats, carnosine has proved to protect the brain from damage by alcohol and by ischemia.Ischemia is oxygen deprivation and it is what happens on a large scale during a stroke, and perhaps on a much smaller scale when many tiny, undetected strokes kill brain cells later in life. [Ref]


What is glycation, and why should I care?

Hormones and other protein molecules have to fold in on themselves in their own characteristic shape in order to serve the purpose for which they are being secreted.  The conformation is loosely preserved by hydrogen bonds, which is a kind of half-strength chemical bond responsible for many secondary properties of biochemicals.  But the shape can be distorted by reactions with sugar molecules that fit between the chain links in the protein, creating cross links that distort the molecule.  This is glycation.   Glycation is certainly a symptom of aging. And it may also be a cause, though probably not the deep cause of aging.  The cute but confusing acronym AGE stands for Advanced Glycation Endproduct, and AGEs are associated with Alzheimer’s and perhaps Parkinson’s diseases.

Carnosine is known to inhibit glycation in cell cultures.  So there is some buzz about carnosine as a treatment for neurodegeneration in humans, but to my knowledge there have not been clinical trials.


Warning: it’s also an anti-oxidant

The worst thing you can say about carnosine is that it is an anti-oxidant. It mops up ROS (reactive oxygen species) that are generated in normal cellular energy metabolism. Anti-oxidants have rarely been shown to extend life span, and may have deleterious effects, as I discussed two weeks ago.  The direct effect of anti-oxidants is to prevent damage to delicate biochemicals, but the indirect effects mess with the body’s global signaling.  Apparently, oxidative damage triggers a repair and rebuilding program, and improves insulin sensitivity, so that the net result of oxidative damage can often be positive for long-term health!


Carnosine Promotes Telomerase

The best thing you can say about carnosine is that it signals the cell to rejuvenate itself with telomerase.  It’s my belief that short telomeres are a deep cause of aging, and that activating the body’s own telomerase is one of the most promising anti-aging strategies for the near future.  In this context, carnosine was identified very early as a telomerase promoter.  (I think it may have been the first.)  Several experiments since then have confirmed the rejuvenating effect of carnosine in aging cell cultures.

In terms of theory, the question is always raised, if such a simple molecule could extend life span without detrimental side effects, why wouldn’t the body already be doing this? My answer is that the body doesn’t want to live longer. We (and other animals) are genetically programmed to have the life spans that we have, not because it’s good for our fitness as individuals (of course, it isn’t), but because it promotes population stability in the community.

So such theoretical doubts don’t worry me, but I do wonder whether the effects in our bodies can realize the potential hinted by carnosine’s biochemistry.  Carnosine is well-absorbed from food, but does it get to the cells where it is needed most?  The body is not usually in the business of transporting carnosine in the blood, but rather manufacturing it where and when it is needed, right in the cell.


So – will it help me live longer?

Since controlled experiments with humans are so problematic, the “silver standard” for anti-aging therapies is life extension in rodents. Many substances extend life span in fruitflies, for example, but fail when they get to mice. Carnosine has been tested in “senescence-accelerated mice”, where it extends mean life span by 20%. These mice are bred for shorter life span, and carnosine is able to bring their life spans back toward normal. Maybe that’s the “bronze standard”. This was done with a dosage of 100mg/Kg of body weight. Scaled up to humans, this would be 10-15 pills daily of the usual 500 mg size*.

I know of no tests of carnosine in normal mice.  Sometimes such studies get done, and they are not published if results are negative.  So the absence of data may be a bad sign.  Recently, Stephen Spindler of UC Riverside reported on experiments with several commercial combinations of supplements, testing to see if they extend life span of mice.  All the results were negative.  One of the formulations contained carnosine.

Spindler has played a role in our community, helping to keep our expectations grounded and down to earth.  I’ll write more about the study with commercial supplement formulas in coming weeks.

Carnosine has been promoted as an anti-aging supplement for at least 15 years, but confirmation of its benefits either in humans or in mice has not kept up.  Whether it works as advertised remains to be seen.



* But even this is controversial. There is no agreement how to scale dosages for small animals to equivalents for humans, because some argue that the rate of metabolism should be taken into account, in addition to body weight. This would lower the equivalent human dose.