Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria

Samuel E. Schriner, Nancy J. Linford, George M. Martin, Piper Treuting, Charles E. Ogburn, Mary Emond, Pinar E. Coskun, Warren Ladiges, Norman Wolf, Holly Van Remmen, Douglas C. Wallace, Peter S. Rabinovitch

Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA.
Department of Pathology, University of Washington, Seattle, WA 91895, USA.
Department of Comparative Medicine, University of Washington, Seattle, WA 91895, USA.
Department of Biostatistics, University of Washington, Seattle, WA 91895, USA.
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.
Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX 78229, USA.

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase 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 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.