期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 64, 期 12, 页码 1212-1220出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glp132
关键词
Oxidative stress; Longevity
资金
- The Department of Veterans Affair Merit
- Glenn Foundation
- The National Institute of Health [DK19971]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK019971, R01DK019971] Funding Source: NIH RePORTER
To test the impact of increased mitochondrial oxidative stress as a mechanism underlying aging and age-related pathologies, we generated mice with a combined deficiency in two mitochondrial-localized antioxidant enzymes, Mn superoxide dismutase (MnSOD) and glutathione peroxidase-1 (Gpx-1). We compared life span, pathology, and oxidative damage in Gpx1(-/)-, Sod2(+/)-Gpx1(+/)-, Sod2(+/)-Gpx1(-/)-, and wild-type control mice. Oxidative damage was elevated in Sod2(+/)-Gpx1(-/)-mice, as shown by increased DNA oxidation in liver and skeletal muscle and increased protein oxidation in brain. Surprisingly, Sod2(+/)-Gpx1(-/)- mice showed no reduction in life span, despite increased levels of oxidative damage. Consistent with the important role for oxidative stress in tumorigenesis during aging, the incidence of neoplasms was significantly increased in the older Sod2(+/)-Gpx1(-/)-mice (28-30 months). Thus, these data do not support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice and do not support the oxidative stress theory of aging.
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