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.

 

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* 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.


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5 thoughts on “A Well-known Anti-aging Supplement”

  1. I believe that the term AGE (advanced glycation end-products) came from Anthony Cerami – when he was at Rockefeller U. He came up with that catchy name because he was starting a company to capitalize on his work – and he and a chemist discovered a compound which was called ALT711 (subsequently changed but maybe someone could find out its status) that cleaved AGE-products in situ (where they were) – and was safe for human use. I’m wondering if anyone else has knowledge of this? If true (if it worked as described (Tony came up with this idea because as a physician with particular interest in diabetes, he wondered about the cause of the premature aging seen in diabetics. He connected it with extended periods of high blood sugar causing the formation of glycated proteins (they now test for glycated hemoglobin (Hb A1C – or just A1C). After a while a further reaction causes the formation of AGE products which are not supposed to be reversible and contribute to phenomena like the intrinsic hypertension (high blood pressure) seen in the elderly.

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  2. Good post! I didn’t know carnosine stimulated telomerase. I take beta alanine pre workout because it aids in musc strength, and to cont ages, I also take lipoid acid for that. I want looooong telomeres!

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