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

Samuel E. Schriner(University of Washington), Nancy J. Linford(University of Washington), George M. Martin(University of Washington), Piper M. Treuting(University of Washington), Charles E. Ogburn(University of Washington), Mary J. Emond(University of Washington), Pınar Coşkun(University of Washington), Warren Ladiges(University of Washington), Norman S. Wolf(University of Washington), Holly Van Remmen(The University of Texas at San Antonio Health Science Center), Douglas C. Wallace(University of Washington), Peter S. Rabinovitch(University of Washington)
Science
May 6, 2005
Cited by 1,719

Abstract

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.


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