Nutrition, oxidative damage, telomere shortening, and cellular senescence:Individual or connected agents of aging?

There is substantial and long-standing literature linking the level of gene ral nutrition to longevity. Reducing nutrition below the amount needed to s ustain maximum growth increases longevity in a wide range of organisms. Oxi dative damage has been shown to be a major feature of the aging process. Te lomere shortening is now well established as a key process regulating cell senescence in vitro. There is some evidence that the same process may be im portant for aging in vivo. Very recently it has been found that oxidative d amage accelerates telomere shortening. It is therefore possible for us to p ropose as an outline hypothesis that the level of nutrition determines oxid ative damage which in turn determines telomere shortening and cell senescen ce and that this pathway is important in determining aging and longevity in vivo. We also propose that telomeres in addition to their well-recognized role in "counting" cell divisions are also, through their GGG sequence, imp ortant monitors of oxidative damage over the life span of a cell. This may explain the evolutionary conservations of this triplet in the repeat telome re sequence unit. (C) 2000 Academic Press.