Oxidative stress, caloric restriction, and aging

Abstract

Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of an imbalance between prooxidants and antioxidants. The amount of oxidative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster. (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical (O2) and hydrogen peroxide. (iii) Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.

Figures

Fig. 1

Effect of overexpression of antioxidative enzymes on life-span and protein oxidative damage in D. melanogaster. Survival curves (solid) and protein carbonyl content (dashed curves) at different ages for a control group (blue triangles) and three different lines (remaining symbols) of transgenic D. melanogaster overexpressing both Cu.Zn-superoxide dismutase and catalase. [Adapted from (23)]

Fig. 2

Comparison of maximum life-span (MLS) with (A) metabolic rate and rate of O2⋅− generation in submitochondrial particles, (B) total superoxide dismutase activity, and (C) glutathione peroxidase activity, in the heart of different mammalian species. [Adapted from (4) and (29)] MLS shows an inverse relation to metabolic rate (reported as calories consumed per gram of body weight per day) and O2⋅− generation, but no relation to antioxidative enzyme activity.

Fig. 3

Effect of caloric intake on (A) body weight, (B) percent survival, and (C) life-span in female C3B10F1, mice. Symbols in (A) apply to (B) as well. [Adapted from (38)]