Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging.

TitleMitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging.
Publication TypeJournal Article
Year of Publication2005
AuthorsKujoth, GC, Hiona, A, Pugh, TD, Someya, S, Panzer, K, Wohlgemuth, SE, Hofer, T, Seo, AY, Sullivan, R, Jobling, WA, Morrow, JD, Van Remmen, H, Sedivy, JM, Yamasoba, T, Tanokura, M, Weindruch, R, Leeuwenburgh, C, Prolla, TA
JournalScience
Volume309
Issue5733
Pagination481-4
Date Published2005 Jul 15
ISSN1095-9203
KeywordsAging, Amino Acid Substitution, Animals, Apoptosis, Caspase 3, Caspases, Cloning, Molecular, DNA Damage, DNA Fragmentation, DNA Polymerase gamma, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Gene Targeting, Humans, Hydrogen Peroxide, Lipid Peroxidation, Liver, Mice, Mitochondria, Heart, Mitochondria, Liver, Muscle, Skeletal, Mutation, Myocardium, Oxidative Stress, Phenotype, Presbycusis, Reactive Oxygen Species
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.

DOI10.1126/science.1112125
Alternate JournalScience
Citation Key10.1126/science.1112125
PubMed ID16020738
Grant ListAG021905 / AG / NIA NIH HHS / United States
AG16694 / AG / NIA NIH HHS / United States
AG17994 / AG / NIA NIH HHS / United States
AG18922 / AG / NIA NIH HHS / United States
AG21042 / AG / NIA NIH HHS / United States
DK48831 / DK / NIDDK NIH HHS / United States
RR00095 / RR / NCRR NIH HHS / United States
T32 AG00213 / AG / NIA NIH HHS / United States
T32 GM07601 / GM / NIGMS NIH HHS / United States