期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 62, 期 9, 页码 932-942出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/62.9.932
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资金
- NIA NIH HHS [P01AG020591, P01 AG19316, P30-AG13319] Funding Source: Medline
- NIGMS NIH HHS [R37GM42056] Funding Source: Medline
Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme that plays an important role in detoxification of oxidative damage to membrane lipids. Because oxidative stress is proposed to play a causal role in aging, we compared the life spans of Gpx4 heterozygous knockout mice (Gpx4(+/-) mice) and wild-type mice (WT mice). To our surprise, the median life span of Gpx4(+/-) mice (1029 days) was significantly longer than that of WT mice (963 days) even though the expression of Gpx4 was reduced approximately 50% in all tissues of Gpx4(+/-) mice. Pathological analysis revealed that Gpx4(+/-) mice showed a delayed occurrence of fatal tumor lymphoma and a reduced severity of glomerulonephritis. Compared to WT mice, Gpx4(+/-) mice showed significantly increased sensitivity to oxidative stress-induced apoptosis. Our data indicate that lifelong reduction in Gpx4 increased life span and reduced/retarded age-related pathology most likely through alterations in sensitivity of tissues to apoptosis.
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