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Science 5 July 1996:
Vol. 273. no. 5271, pp. 59 - 63
DOI: 10.1126/science.273.5271.59
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Articles

Oxidative Stress, Caloric Restriction, and Aging

Rajindar S. Sohal * and Richard Weindruch *

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 (O·-2) 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.

R. S. Sohal is in the Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA. R. Weindruch is in the Department of Medicine and Veterans Administration Geriatric Research, Education and Clinical Center, University of Wisconsin, Madison, WI 53705, USA.
* Both authors contributed equally to this work, and correspondence may be directed to either author.


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