Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging

Gregory C. Kujoth(University of Wisconsin–Madison), Asimina Hiona(University of Wisconsin–Madison), Thomas D. Pugh(University of Wisconsin–Madison), Shinichi Someya(University of Wisconsin–Madison), K. Panzer(University of Wisconsin–Madison), Stephanie E. Wohlgemuth(University of Wisconsin–Madison), Tim Hofer(University of Wisconsin–Madison), Arnold Y. Seo(University of Wisconsin–Madison), Rachel Sullivan(University of Wisconsin–Madison), Wendy A. Jobling(University of Wisconsin–Madison), Jason D. Morrow(University of Wisconsin–Madison), Holly Van Remmen(University of Wisconsin–Madison), John M. Sedivy(University of Wisconsin–Madison), Tatsuya Yamasoba(University of Wisconsin–Madison), Masaru Tanokura(University of Wisconsin–Madison), Richard Weindruch(University of Wisconsin–Madison), Christiaan Leeuwenburgh(University of Wisconsin–Madison), Tomas A. Prolla(University of Wisconsin–Madison)
Science
July 14, 2005
10.1126/science.1112125
Cited by 2,153

Abstract

Mutations in mitochondrial DNA (mtDNA) accumulate in tissues of mammalian species and have been hypothesized to contribute to aging. We show that mice expressing a proofreading-deficient version of the mitochondrial DNA polymerase g (POLG) accumulate mtDNA mutations and display features of accelerated aging. Accumulation of mtDNA mutations was not associated with increased markers of oxidative stress or a defect in cellular proliferation, but was correlated with the induction of apoptotic markers, particularly in tissues characterized by rapid cellular turnover. The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.

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