OXIDATIVE STRESS, CALORIC RESTRICTION, AND AGING

Under normal physiological conditions, the use of oxygen by cells of a erobic organisms generates potentially deleterious reactive oxygen met abolites. A chronic state of oxidative stress exists In cells because of an imbalance between prooxidants and antioxidants. The amount of ox idative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includ es the following observations: (i) Overexpression of antioxidative enz ymes retards the age-related accrual of oxidative damage and extends t he maximum life-span of transgenic Drosophila melanogaster. (ii) Varia tions in longevity among different species inversely correlate with th e rates of mitochondrial generation of the superoxide anion radical (O -2(-)) and hydrogen peroxide, (iii) Restriction of caloric intake lowe rs steady-state levels of oxidative stress and damage, retards age-ass ociated changes, and extends the maximum life-span in mammals.