Document Detail

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.
MedLine Citation:
PMID:  21368114     Owner:  NLM     Status:  MEDLINE    
A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.
Adeel Safdar; Jacqueline M Bourgeois; Daniel I Ogborn; Jonathan P Little; Bart P Hettinga; Mahmood Akhtar; James E Thompson; Simon Melov; Nicholas J Mocellin; Gregory C Kujoth; Tomas A Prolla; Mark A Tarnopolsky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-22
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-09     Completed Date:  2011-05-26     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4135-40     Citation Subset:  IM    
Department of Kinesiology, McMaster University, Hamilton, ON, Canada L8N 3Z5.
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MeSH Terms
Aging / genetics,  physiology*
DNA, Mitochondrial / genetics*
Gene Dosage
Mice, Mutant Strains
Mitochondria / physiology*
Oxidative Stress
Physical Conditioning, Animal*
Physical Endurance*
Point Mutation*
Grant Support
MOP97805//Canadian Institutes of Health Research; P30AG025708/AG/NIA NIH HHS
Reg. No./Substance:
0/DNA, Mitochondrial

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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