Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice
Edited by Bruce M. Spiegelman, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA 02115, and approved January 28, 2011 (received for review December 30, 2010)
Abstract
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.
Acknowledgments
This work was supported by the Canadian Institutes of Health Research (Grant MOP97805), a kind donation from Mr. Warren Lammert and family (to M.A.T.), and Nathan Shock Award P30AG025708 (to S.M.). A.S. is funded by a Canadian Institutes of Health Research Institute of Aging doctoral research scholarship and a Canada PRESTIGE fellowship. D.I.O. and J.P.L. are funded by National Sciences and Engineering Research Council scholarships. G.C.K. and T.A.P. were awarded US Patent 7,126,040 for the PolgD257A mouse.
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Published online: February 22, 2011
Published in issue: March 8, 2011
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Acknowledgments
This work was supported by the Canadian Institutes of Health Research (Grant MOP97805), a kind donation from Mr. Warren Lammert and family (to M.A.T.), and Nathan Shock Award P30AG025708 (to S.M.). A.S. is funded by a Canadian Institutes of Health Research Institute of Aging doctoral research scholarship and a Canada PRESTIGE fellowship. D.I.O. and J.P.L. are funded by National Sciences and Engineering Research Council scholarships. G.C.K. and T.A.P. were awarded US Patent 7,126,040 for the PolgD257A mouse.
Notes
*This Direct Submission article had a prearranged editor.
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The authors declare no conflict of interest.
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