Mice Deficient in Both Mn Superoxide Dismutase and Glutathione Peroxidase-1 Have Increased Oxidative Damage and a Greater Incidence of Pathology but No Reduction in Longevity

被引：146

作者：

Zhang, Yiqiang ^{[1
,2
]}

Ikeno, Yuji ^{[1
,3
,4
,5
]}

Qi, Wenbo ^{[1
]}

Chaudhuri, Asish ^{[1
,3
,6
]}

Li, Yan ^{[1
]}

Bokov, Alex ^{[1
,5
]}

Thorpe, Suzanne R. ^{[7
]}

Baynes, John W. ^{[7
,8
]}

Epstein, Charles ^{[9
,10
]}

Richardson, Arlan ^{[1
,2
,3
,5
]}

Van Remmen, Holly ^{[1
,2
,3
,5
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA

[3] S Texas Vet Hlth Care Syst, San Antonio, TX USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78245 USA

[5] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78245 USA

[7] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA

[8] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA

[9] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2009年 / 64卷 / 12期

关键词：

Oxidative stress; Longevity; LIFE-SPAN; MITOCHONDRIAL-FUNCTION; INCREASED SENSITIVITY; CALORIC RESTRICTION; MUTANT MICE; KNOCKOUT; STRESS; OVEREXPRESSION; EXTENSION; LACKING;

D O I：

10.1093/gerona/glp132

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页码：1212 / 1220

页数：9

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