Oxidatively Modified Proteins and Maintenance Systems as Biomarkers of Aging

Abstract

The accumulation of non-functional oxidized proteins is a hallmark of aging both in cells and in the body. This age-related build-up of proteins modified by oxidative processes results, at least in part, from an increase in reactive oxygen species and other toxic compounds from both cellular metabolism and external environmental factors. Failure of protein maintenance (i.e. oxidized protein degradation and repair) is another major contributor to the age-associated accumulation of damaged proteins. Oxidative damage to the cellular proteome, leading to the formation of carbonylated proteins derives from the direct oxidation of several amino acids side chains and also through protein adducts formation with lipid peroxidation products and dicarbonyl glycating compounds. Since the accumulation of oxidatively damaged proteins is believed to participate to the age-related decline in cellular function, their identification has been achieved in human or mammalian animal models of aging and age-related diseases as well as in human fibroblasts and myoblasts during cellular senescence and upon oxidative stress. Indeed, the identification of damaged protein targets is expected not only to define potential biomarkers of aging but also to give insight into the mechanisms by which these damaged proteins accumulate and may contribute to cellular dysfunction.