Age-associated, oxidatively modified proteins: A critical evaluation

Reactive oxygen species have been implicated in oxidative modifications of proteins, in many cases represented as carbonyls, which can lead to a variety of diseases and the age-associated decline of physiological functions. Considerable progress, as well as controversy, about oxidatively modified proteins and aging has unfolded in the last few years. In this article we critically evaluate changes in protein carbonyl content as a marker of the oxidative stress associated with age and other relevant issues on the degradation of oxidatively modified proteins. A definitive conclusion on the age-related increase of protein carbonyls is currently viewed as having to await further confirmation using detailed analysis with new methodologies. Controversial methodological measurements and characterizations of protein carbonyls are discussed, emphasizing the merits of immunoblot analysis using two-dimensional gel electrophoresis. The degradation of oxidatively modified proteins has not yet been studied in depth in relation to their possible accumulation in old tissues. Recent efforts to establish a causal relation between the effect of oxidative stress on proteins and physiological declines with age are discussed briefly.