Racemization of aspartic acid in human proteins.

Aspartic acid racemization (AAR) represents one of the major types of non-enzymatic covalent modification that leads to an age-dependent accumulation of abnormal protein in numerous human tissues. In vivo racemization is an autonomic process during the "natural" ageing of proteins, and correlates with the age of long-lived proteins. Consequently AAR can be used as molecular indicator of protein ageing as well as for the identification of permanent proteins that age with the human organism. Although long-living, structural proteins are mainly affected, AAR may be significant on a time scale also relevant to enzymes and signaling proteins. It may result in a loss of protein function due to proteolysis or due to changes in the molecular structure. In vivo racemization may also increase in pathological conditions. AAR has already been discussed as a relevant pathophysiological factor in the pathogenesis of diseases of old age such as atherosclerosis, lung emphysema, presbyopia, cataract, degenerative diseases of cartilage and cerebral age-related dysfunctions. Although the details of the biological consequences of AAR have to be further elucidated, it is evident that AAR plays a role in the molecular biology of ageing.