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Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria
Samuel E. Schriner,1,5Nancy J. Linford,2George M. Martin,1,2Piper Treuting,3Charles E. Ogburn,2Mary Emond,4Pinar E. Coskun,5Warren Ladiges,3Norman Wolf,2Holly Van Remmen,6Douglas C. Wallace,5Peter S. Rabinovitch2*
To determine the role of reactive oxygen species in mammalianlongevity, we generated transgenic mice that overexpress humancatalase localized to the peroxisome, the nucleus, or mitochondria(MCAT). Median and maximum life spans were maximally increased(averages of 5 months and 5.5 months, respectively) in MCATanimals. Cardiac pathology and cataract development were delayed,oxidative damage was reduced, H2O2 production and H2O2-inducedaconitase inactivation were attenuated, and the developmentof mitochondrial deletions was reduced. These results supportthe free radical theory of aging and reinforce the importanceof mitochondria as a source of these radicals.
1 Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA. 2 Department of Pathology, University of Washington, Seattle, WA 91895, USA. 3 Department of Comparative Medicine, University of Washington, Seattle, WA 91895, USA. 4 Department of Biostatistics, University of Washington, Seattle, WA 91895, USA. 5 Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry and Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA 92697, USA. 6 Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX 78229, USA.
* To whom correspondence should be addressed. E-mail: petersr{at}u.washington.edu
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Richard A. Miller (24 June 2005) Science308 (5730), 1875.
[DOI: 10.1126/science.1114393] |Summary »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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280, 41057-41068
|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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