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Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.

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.

SUBMITTER: Safdar A

PROVIDER: S-EPMC3053975 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.

Safdar Adeel A Safdar Adeel A Bourgeois Jacqueline M JM Ogborn Daniel I DI Little Jonathan P JP Hettinga Bart P BP Akhtar Mahmood M Thompson James E JE Melov Simon S Mocellin Nicholas J NJ Kujoth Gregory C GC Prolla Tomas A TA Tarnopolsky Mark A MA

Proceedings of the National Academy of Sciences of the United States of America 20110222 10

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 dis ...[more]

PMID: 21368114

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Project description:BackgroundAge-related hyperkyphosis is multifactorial and involves alterations of vertebral bone, intervertebral discs (IVD) and paraspinal muscles. The relative contribution of these tissues remains unclear. Here, we compared differences in vertebral bone microarchitecture and IVD thickness between prematurely aging mice with spinal hyperkyphosis and wild type littermates.MethodsThoracolumbar vertebral columns were dissected from homozygous Polg D257A and age-matched wild type littermates. Micro-computed tomography was performed to quantify cortical and trabecular bone parameters at anterior and posterior portions of T8-L4 vertebrae. In addition, vertebral shape, transaxial facet joint orientation and IVD thickness were quantified. Differences in anterior/posterior ratios between genotypes were compared by Student's t-test and association between vertebral bone and IVD parameters was investigated using Pearson correlation analysis.ResultsHyperkyphotic homozygous mice displayed generalized osteopenia that was more pronounced at the posterior compared with anterior portion of thoracolumbar vertebrae. An increase in the anterior/posterior ratio of trabecular bone parameters was revealed at the thoracolumbar junction (T13-L1). Polg D257A displayed diffuse loss of cortical bone thickness, yet anterior/posterior ratios were unchanged. Despite generalized and regional bone loss, vertebral shape was unaffected. PolG D257A mice showed a 10-20 % reduction of IVD thickness at both thoracic and lumbar levels, with only minimal histopathological changes. IVD thickness was negatively correlated with anterior/posterior ratios of trabecular bone parameters, as well as with more coronally oriented facet joints, but negatively correlated with the anterior/posterior ratio of cortical bone thickness.ConclusionsAging-induced regional changes of vertebral trabecular and cortical bone did not lead to altered vertebral shape in Polg D257A mice but may indirectly cause hyperkyphosis through reduction of IVD thickness. These findings suggest a limited role for aging-induced bone loss in spinal hyperkyphosis and warrants further research on the involvement of paraspinal muscle degeneration.

Dataset Information

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.

Publications

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.

Similar Datasets

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