L-Carnosine is a dipeptide consisting of of ß-alanine linked at its carboxyl terminus to the amino group of L-histidine (ß-alanyl-L-histidine). It is synthesized by the enzyme carnosine synthetase, and broken down by carnosinase. It is widely distributed in tissues, and is present at particularly high concentrations in skeletal muscle and the olfactory lobe of the brain. Carnosine has a number of important properties, including antioxidant activity, ability to chelate divalent cations such as copper, neutralization of acids (such as lactic acid), and the inhibition of nonenzymic glycosylation of proteins. It is found in long-lived tissues in surprisingly high amounts (up to 20 mM in human muscle) and has been shown to delay aging in cultured cells. When added to cultures of human lung and foreskin fibroblasts, the dipeptide extended cell survival and increased maximal cell division potential while also inducing a more juvenile phenotype in senescent human and rodent cells. This suggests that other properties of the dipeptide are involved. There are suggestions that the concentration of tissue-associated L-carnosine declines with age. L-Carnosine and related dipeptides have been shown to prevent peroxidation of model membrane systems, suggesting that they represent water-soluble counterparts to lipid-soluble antioxidants such as a-tocopherol in protecting cell membranes from oxidative damage. Other roles ascribed to this dipeptide include acting as a neurotransmitter in the modulation of enzyme activities.
L-Carnosine significantly reduces the formation of 8-hydroxy deoxyguanosine (8-OH dG) in cultured cells, thus demonstrating protection of DNA. The presumptive anti-senescent effect of L-carnosine may be related to this inhibition. L-Carnosine also inhibits protein carbonyl formation. A common molecular indication of cellular aging is the accumulation of aberrant proteins, especially polypeptides bearing carbonyl (CO) groups.