AGE-ASSOCIATED, OXIDATIVELY MODIFIED PROTEINS - A CRITICAL-EVALUATION

Reactive oxygen species have been implicated in oxidative modification s of proteins, in many cases represented as carbonyls, which can lead to a variety of diseases and the age-associated decline of physiologic al functions. Considerable progress, as well as controversy, about oxi datively modified proteins and aging has unfolded in the last few year s. In this article we critically evaluate changes in protein carbonyl content as a marker of the oxidative stress associated with age and ot her relevant issues on the degradation of oxidatively modified protein s. A definitive conclusion on the age-related increase of protein carb onyls is currently viewed as having to await further confirmation usin g detailed analysis with new methodologies. Controversial methodologic al measurements and characterizations of protein carbonyls are discuss ed, emphasizing the merits of immunoblot analysis using two-dimensiona l gel electrophoresis. The degradation of oxidatively modified protein s has not yet been studied in depth in relation to their possible accu mulation 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.