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Published Online May 5, 2005
Science DOI: 10.1126/science.1106653

Reports

Submitted on October 22, 2004
Accepted on April 15, 2005

Extension of Murine Lifespan by Overexpression of Catalase Targeted to Mitochondria

Samuel E. Schriner 1, Nancy J. Linford 2, George M. Martin 3, Piper Treuting 4, Charles E. Ogburn 2, Mary Emond 5, Pinar E. Coskun 6, Warren Ladiges 4, Norman Wolf 2, Holly Van Remmen 7, Douglas C. Wallace 6, Peter S. Rabinovitch 8*

1 Departments of Genome Sciences; Center for Molecular and Mitochondrial Medicine and Genetics, Departments of Biological Chemistry and Ecology and Evolutionary Biology, University of California, Irvine, Irvine CA 92697, USA.
2 Departments of Pathology
3 Departments of Genome Sciences; Pathology
4 Departments of Comparative Medicine
5 Department of Biostatistics, University of Washington, Seattle, WA 91895, USA.
6 Center for Molecular and Mitochondrial Medicine and Genetics, Departments of Biological Chemistry and Ecology and Evolutionary Biology, University of California, Irvine, Irvine CA 92697, USA.
7 Dept. of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio TX 78229, USA.
8 Department of Pathology

* To whom correspondence should be addressed.
Peter S. Rabinovitch , E-mail: E-mail: petersr{at}u.washington.edu

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). Median and maximum lifespans were maximally increased (average 5 months, and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.


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