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 general nutrition to longevity. Reducing nutrition below the amount needed to sustain maximum growth increases longevity in a wide range of organisms. Oxidative damage has been shown to be a major feature of the aging process. Telomere shortening is now well established as a key process regulating cell senescence in vitro. There is some evidence that the same process may be important for aging in vivo. Very recently it has been found that oxidative damage accelerates telomere shortening. It is therefore possible for us to propose as an outline hypothesis that the level of nutrition determines oxidative damage which in turn determines telomere shortening and cell senescence 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, important monitors of oxidative damage over the life span of a cell. This may explain the evolutionary conservations of this triplet in the repeat telomere sequence unit.