Oxidative modification of proteins during aging

Abstract

Accumulating experimental evidence supports the proposal that many of the changes which occur during aging are a consequence of oxidative damage. Reactive oxygen species react with all three of the major cellular macromolecules, nucleic acids, lipids, and proteins. This minireview focuses on proteins as targets of oxidizing species during aging. Many of the reactions mediated by these oxidizing species result in the introduction of carbonyl groups into proteins. The steady-state level of carbonyl-bearing proteins increases exponentially during the last third of lifespan in animals ranging from C. elegans to man. Genetic and non-genetic manipulations which lengthen lifespan cause a decrease in the level of protein carbonyl while those which shorten lifespan increase the level. Oxidized proteins bearing carbonyl groups are generally dysfunctional, and in the last third of lifespan the content of these oxidized proteins rises to a level likely to cause substantial disruption of cellular function.