The Anti-Aging Effects of Carnosine
Proteins are the substances most responsible for the daily functioning of living organisms. Destruction to proteins can be caused by oxidation (as by free radicals) and protein-sugar reactions (glycation). Once too many proteins lose their ability to function, the body becomes prone to degenerative diseases and premature aging.1 Carnosine, an amino acid compound, has been shown to specifically protect against the age-related degradation of protein.
Carnosine quenches the most destructive protein-oxidizing agent (the hydroxyl radical). One study showed carnosine was the only antioxidant to significantly protect cellular chromosomes from oxidative damage.2 Antioxidants cannot completely protect proteins. Nature's second line of defense is to repair or remove damaged proteins.3 This is where carnosine demonstrates its most profound anti-aging effect.
Protein degradation occurs as a result of cross-linking and the formation of advanced glycation end products (AGE). These changes figure prominently in the processes of aging and its typical signs such as skin wrinkling and brain degeneration.4,5 Studies show that carnosine is effective against cross-linking and the formation of advanced glycation end products (AGE).6,7 Glycated proteins produce 50-fold more free radicals than nonglycated proteins and carnosine may be the most effective anti-glycating agent known.
An example of carnosine's defense against protein degradation is provided by MDA (malondialdehyde).8 MDA causes protein cross-linking and AGE formation. Carnosine has been shown to inhibit MDA-induced glycation in blood albumin and eye lens protein.9 Carnosine has also been shown to keep MDA from inducing protein cross-linking.10 One study showed that carnosine actually decreased MDA levels in mice.
Carnosine is highly concentrated in the brain. The reason is that the brain uses carnosine to protect against cross-linking, glycation, excitotoxicity and oxidation. Animal studies show that carnosine provides broad protective effects in simulated ischemic stroke.11
Abnormal copper and zinc metabolism stimulates senile plaque formation in Alzheimer's disease. Chelators of these metals dissolve plaques in the laboratory. Carnosine is a potent copper-zinc chelating agent that can inhibit the cross-linking of amyloid-beta that leads to brain cell plaque formation. A signature of Alzheimer's disease is impairment of brain arterial and capillary system. Carnosine has been shown to protect the cells that line brain blood vessels from damage by amyloid-beta as well as byproducts of lipid oxidation and alcohol metabolism.12
Carnosine extends cellular life span
Our bodies are comprised of cells that replace themselves by dividing. There is a genetic limit as to how many times our cells will continue to replicate themselves via healthy division processes. Once enough cells reach their genetic reproductive limit, the organism (our body) is no longer able to sustain life functions and succumbs to disease or death. Carnosine appears to extend the period of time that cells will continue to divide in a youthful manner.
Laboratory research suggests that carnosine has the ability to rejuvenate cells approaching the end of the life cycle of dividing cells, restoring normal appearance and extending cellular life span.13 When scientists transferred late-passage fibroblasts (a type of skin cell) to a culture medium containing carnosine, they exhibited a rejuvenated appearance and often an enhanced capacity to divide.14 The carnosine medium increased life span, even for old cells. Cells transferred to the carnosine medium attained a life span of 413 days, compared to 126 to 139 days for the control cells. This study showed that carnosine induced a remarkable 67% increase in cellular life span.
These aged cells also grew in the characteristic patterns of young cells, and resumed a uniform appearance in the presence of carnosine. But when they transferred the aged cells back to a medium lacking carnosine, the signs of senescence quickly reappeared. The scientists switched late-passage cells back and forth several times between the culture media. Carnosine consistently restored the youthful cell phenotype within days, whereas the standard culture medium (without carnosine) brought back the senescence cell phenotype. How does carnosine revitalize cells in culture? Some researchers propose that carnosine may rejuvenate cells by reducing the formation of abnormal proteins, or by stimulating the removal of old proteins.9
Carnosine extends organism life span
A study tested the effect of carnosine on life span and indicators of aging in senescence-accelerated mice. Carnosine extended the life span of the treated mice by 20% on average, compared to the mice not fed carnosine.15 The mice given carnosine were about twice as likely to reach the "ripe old age" of 12 months as untreated mice.
Carnosine did not alter the 15 month maximum life span of the senescence-accelerated mouse strain, but it did significantly raise the number of mice surviving to old age. Carnosine distinctly improved the appearance of the aged mice, whose coat fullness and color remained much closer to that of young animals. Significantly more carnosine-treated mice had glossy coats (44% vs. 5%), while fewer had skin ulcers (14% vs. 36%).
The researchers also measured biochemical indicators associated with brain aging. Carnosine treated mice had significantly lower levels of toxic MDA (malondialdehyde) in their brain cell membranes. MAO-B (monoamine oxidase B) activity was 44% lower in the carnosine-treated mice, indicating maintenance of youthful dopamine metabolism. Aging humans produce too much MAO-B, and this is thought to contribute to certain types of brain cell damage. Glutamate binding to its cellular receptors nearly doubled in the carnosine treated group, which may explain the more normal behavioral reactivity of the carnosine-fed mice.
This longevity study showed that carnosine significantly improved most measures of appearance, physiological health, behavior, and brain biochemistry, as well as extending life span. The researchers concluded that "carnosine-treated animals can be characterized as more resistant to the development of features of aging."
Carnosine chelates copper and zinc
Copper and zinc are neurological double-edged swords. While the body cannot live without them, new research confirms that they can also be neurotoxic. Abnormal copper-zinc metabolism is implicated in Alzheimer's disease, stroke, seizures, and many other diseases with neurological components. Copper and zinc appear to be needed to modulate synaptic transmission, but can become neurotoxins at the concentrations reached when they are released from synaptic terminals. The brain must buffer these metals so that they can perform their functions without neurotoxicity. The new research on copper-zinc toxicity shows that carnosine provides that buffering action.16 When scientists exposed rat neurons to physiological concentrations of copper or zinc the neurons died. However carnosine at a modest physiological concentration protected the neurons from the toxic effects of these metals.
A spate of recent research papers point to the role of abnormal copper and zinc metabolism in the development of Alzheimer's disease. This abnormal copper and zinc metabolism contributes to amyloid-beta formation and toxicity through a host of mechanisms.17,18 These findings on copper and zinc as Alzheimer's disease promoters led scientists to investigate the effect of metal chelators on amyloid-beta plaques. A recent laboratory experiment by an international team of scientists found that chelators of copper and zinc solubilize (dissolve) aggregates of amyloid-beta in post-mortem human tissue samples from the brains of Alzheimer's disease patients.19 They hypothesize that:
Carnosine fits this metal chelating profile, offering pH buffering and hydroxyl radical scavenging actions in addition. Not only does carnosine chelate copper and zinc, but the presence of copper and zinc ions enhances carnosine's potency as a scavenger of the superoxide radical.20
Microvascular damage is the harbinger of Alzheimer's disease, preceding its other pathological features, possibly by impairing delivery of nutrients to the brain.21 An experiment on rat brain blood vessel walls shows that carnosine prevents this damage.12 In another experiment carried out by the same British team, carnosine protected brain blood vessel cells from damage by MDA (malondialdehyde), a toxic product of lipid peroxidation. Carnosine inhibited protein cross-linking, while protecting cellular and mitochondrial function.22 A third experiment showed that carnosine also protects cells against the toxicity of acetaldehyde, which is produced when alcohol is metabolized.12
Continued on Page 2 of 2