| Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. | |
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MedLine Citation:
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PMID: 21368114 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-22 |
Journal Detail:
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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:
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Created Date: 2011-03-09 Completed Date: 2011-05-26 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 4135-40 Citation Subset: IM |
Affiliation:
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Department of Kinesiology, McMaster University, Hamilton, ON, Canada L8N 3Z5. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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genetics,
physiology* Animals Apoptosis DNA, Mitochondrial / genetics* Gene Dosage Mice Mice, Mutant Strains Mitochondria / physiology* Oxidative Stress Physical Conditioning, Animal* Physical Endurance* Point Mutation* |
| Grant Support | |
ID/Acronym/Agency:
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MOP97805//Canadian Institutes of Health Research; P30AG025708/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Mitochondrial |
| Comments/Corrections | |
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