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CarnosineNature's pluripotent life extension agent
Karin Granstrom Jordan, M.D.
A substance that protects and extends the functional life of the body's key building blocks—cells, proteins, DNA, lipids—can be fairly called an agent of longevity. When that agent is safe, naturally present in the body and in food, and has demonstrated prolongation of life span in animals and cultured human cells, it is fundamental to any life extension program. Mounting research suggests that carnosine has just such anti-aging potential.
Carnosine is a multifunctional dipeptide made up of a chemical combination of the amino acids beta-alanine and l-histidine. Long-lived cells such as nerve cells (neurons) and muscle cells (myocytes) contain high levels of carnosine. Muscle levels of carnosine correlate with the maximum life spans of animal species (Hipkiss AR et al., 1995).
Laboratory research on cellular senescence (the end of the life cycle of dividing cells) suggests that these facts may not be coincidences. Carnosine has the remarkable ability to rejuvenate cells approaching senescence, restoring normal appearance and extending cellular life span.
How does carnosine rejuvenate cells? We do not yet know the full answer, but carnosine's properties may point up key mechanisms of tissue and cell aging, as well as the anti-aging measures that counteract them.
As an antioxidant, Carnosine potently quenches that most destructive of free radicals, the hydroxyl radical, as well as superoxide, singlet oxygen and the peroxyl radical. Surprisingly, carnosine was the only antioxidant to significantly protect chromosomes from oxidative damage due to 90% oxygen exposure.
Carnosine's ability to rejuvenate connective tissue cells may explain its beneficial effects on wound healing. In addition, skin aging is bound up with protein modification. Damaged proteins accumulate and cross-link in the skin, causing wrinkles and loss of elasticity. In the lens of the eye, protein cross-linking is part of cataract formation. Carnosine eye drops have been shown to delay vision senescence in humans, being effective in 100% of cases of primary senile cataract and 80% of cases of mature senile cataract (Wang AM et al., 2000).
Carnosine levels decline with age. Muscle levels decline 63% from age 10 to age 70, which may account for the normal age-related decline in muscle mass and function (Stuerenberg HJ et al., 1999). Since carnosine acts as a pH buffer, it can keep on protecting muscle cell membranes from oxidation under the acidic conditions of muscular exertion. Carnosine enables the heart muscle to contract more efficiently through enhancement of calcium response in heart myocytes (Zaloga GP et al., 1997).
The body is made up largely of proteins. Unfortunately, proteins tend to undergo destructive changes as we age, due largely to oxidation and interactions with sugars or aldehydes. The high levels of Carnosine in the brain may serve as natural protection against excitotoxicity, copper and zinc toxicity, protein cross-linking and glycation, and especially oxidation of cell membranes. Animal studies show broad protective effects in simulated stroke.
New research shows that copper and zinc dramatically stimulate senile plaque formation in Alzheimer's disease. Chelators of these metals dissolve plaques in the laboratory. Carnosine can also inhibit the cross-linking of amyloid-beta that leads to plaque formation. A signature of Alzheimer's disease is impairment of brain microvasculature. Carnosine protected the cells that line brain blood vessels (endothelial cells) from damage by amyloid-beta (senile plaque material) as well as by products of lipid oxidation and alcohol metabolism in laboratory experiments.
Now that many are cutting down on meat—the main dietary source of carnosine—supplementation becomes especially important. Carnosine is safe, with no toxicity even at dosages above 500 mg per kilogram of body weight in animal studies (Quinn PJ et al., 1992). It is most fortunate that carnosine is safe at high dosages because the body would neutralize lesser amounts of carnosine. The enzyme carnosinase (Quinn PJ et al., 1992) must be saturated with more Carnosine than it is able to neutralize in order to make free carnosine available to the rest of the body.
There are thought to be many mechanisms responsible for aging. Consequently, an agent must work along many basic pathways of the aging process in order to control it. Scientists have described carnosine as "pluripotent"—active in a multitude of ways, in many tissues and organs (Hipkiss AR, Preston JE et al., 1998). Carnosine's pluripotent life extension potential places it on a par with CoQ10 as a cornerstone of longevity nutrition.
Given the brain's dependence upon glucose for energy metabolism and the unusually high ratio of fructose to glucose in the brain (about 1:4, compared to 1:20 in plasma), it seems likely that carnosine serves as a natural glycation inhibitor in the brain.
We have seen that Carnosine extends life span at the level of the cell and of the organism. It is equally beneficial to dividing cells and non-dividing cells such as neurons. Moreover, like CoQ10, nature appears to have anticipated us in the purposes carnosine naturally serves in the body.
Surpassing the many supplements that address few and limited aging mechanisms, carnosine stands out as the most promising pluripotent life extension discovery since The Life Extension Foundation introduced Coenzyme Q10 to the American public nearly twenty years ago.
Why we need supplemental carnosine
Carnosine levels in the body decline with age. Muscle levels decrease 63% from age 10 to age 70, which may account for the reduction in muscle mass and function seen in aging humans.
Carnosine acts not only as an antioxidant in muscle, but also as a pH buffer. In this way it keeps on protecting muscle cell membranes from oxidation under the acidic conditions of muscular exertion. Carnosine enables the heart muscle to contract more efficiently through enhancement of calcium response in heart cells. Muscle levels of carnosine correlate with the maximum life spans of animal species.
Carnosine's has been shown to rejuvenate connective tissue cells, which may explain its beneficial effects on wound healing. Damaged proteins accumulate and cross-link in the skin, causing wrinkles and loss of elasticity.
Protein cross-linking is also involved in cataract formation. Carnosine has been shown to be effective in the treatment of senile cataracts in dogs, and in the prevention of cataract development in rabbits.
The multiplicity of pathological effects caused by protein degradation places this problem beyond the scope of simple antioxidants. Carnosine is the most promising broad spectrum shield against protein degradation.
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Studies on the rejuvenating effects of carnosine have shown: