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Free Radic Biol Med. 2014 Jun;71:368-78. doi: 10.1016/j.freeradbiomed.2014.03.038. Epub 2014 Apr 4.

Revisiting an age-old question regarding oxidative stress.

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The Sam and Ann Barshop Institute for Longevity and Aging Studies and San Antonio, TX 78229, USA.
The Sam and Ann Barshop Institute for Longevity and Aging Studies and San Antonio, TX 78229, USA; The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address:


Significant advances in maintaining health throughout life can be made through a clear understanding of the fundamental mechanisms that regulate aging. The Oxidative Stress Theory of Aging (OSTA) is probably the most well studied mechanistic theory of aging and suggests that the rate of aging is controlled by accumulation of oxidative damage. To directly test the OSTA, aging has been measured in several lines of mice with genetic alterations in the expression of enzymatic antioxidants. Under its strictest interpretation, these studies do not support the OSTA, as modulation of antioxidant expression does not generally affect mouse life span. However, the incidence of many age-related diseases and pathologies is altered in these models, suggesting that oxidative stress does significantly influence some aspects of the aging process. Further, oxidative stress may affect aging in disparate patterns among tissues or under various environmental conditions. In this review, we summarize the current literature regarding aging in antioxidant mutant mice and offer several interpretations of their support of the OSTA.


Age-related disease; Aging; Free radicals; Life span; Longevity; Mouse models

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