Oxidative stress and aging: the potential role of iron.

According to the free radical theory of aging proposed by Denham Harman more than 50 years ago, oxidatively modified cellular components accumulate continuously in the cells during the organism's lifespan leading to progressive decline of cellular functions. Since then, it has been shown that proteins, lipids, nucleic acids and other cell components undergo reversible and/or irreversible oxidative modifications during aging. Moreover, oxidized cell components can undergo further oxidative modifications leading to formation of products that cell degradation systems are incapable of removing. Accumulation of such non-degradable aggregates further inhibits the functionality of degradation systems, thus aggravating the effects and leading to a vicious cycle. In this presentation, we propose that the availability of intracellular iron in its redox active form (labile iron) represents the main catalyst that mediates extensive oxidative modifications of cellular components and ultimately leads to their accumulation and consequent cellular dysfunction. It is tempting to speculate that regulated restriction of labile iron may have positive effects on health in general and aging in particular.