Medicine: Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging

C. C. Kujoth, A. Hiona, T. D. Pugh, S. Someya, K. Panzer, S. E. Wohlgemuth, T. Hofer, A. Y. Seo, R. Sullivan, W. A. Jobling, J. D. Morrow, H. Van Remmen, J. M. Sedivy, T. Yamasoba, M. Tanokura, R. Weindruch, C. Leeuwenburgh, T. A. Prolla

Research output: Contribution to journalArticlepeer-review

1424 Scopus citations

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 γ (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.

Original languageEnglish (US)
Pages (from-to)481-484
Number of pages4
JournalScience
Volume309
Issue number5733
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Medicine: Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging'. Together they form a unique fingerprint.

Cite this