Reinventing the Wheel: Voluntary Running Promotes Mitochondrial Adaptations in mtDNA Mutator Mouse Model of Aging Conferences uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • The role of mitochondrial abnormalities and mitochondrial DNA (mtDNA) mutagenesis has been extensively characterized in aging. A causal role for mtDNA mutagenesis in aging is supported by recent studies demonstrating that the polymerase gamma (PolG) mutator mouse, harbouring a proofreading‐deficient copy of PolG, exhibits an accelerated aging phenotype, systemic mitochondrial dysfunction, multisystem failure, and reduced lifespan. Longitudinal studies in humans demonstrate that a physically active lifestyle reduces the risk of chronic diseases and increases life expectancy. We aimed to delineate if voluntary wheel running (VOL) can prevent mitochondrial respiratory chain dysfunction and attenuate mitochondrial ultrastructural abnormalities in skeletal muscle of PolG mice. At 3 months of age, 24 PolG mice (♀ = ♂) were randomly assigned to a sedentary (SED) or VOL group. VOL training attenuated the loss of muscle mass (19%) and prevented cardiac hypertrophy (20%) in PolG‐VOL vs. PolG‐SED (P<0.05). VOL training dramatically increased skeletal muscle mtDNA copy number (1.5‐fold), COX activity (75%), and complex‐IV subunit I (2‐fold) and subunit‐IV (1.7‐fold) protein content vs. PolG‐SED (P<0.05). Electron microscopic analysis revealed an atypical accumulation of swollen pleomorphic mitochondria with fragmented cristae and disrupted membranes in the skeletal muscle of PolG‐SED. VOL training reduced these mitochondrial morphological abnormalities in PolG mice. We propose that VOL training promotes mitochondrial capacity and offers a valuable therapeutic intervention for attenuating aging and related morbidity and mortality. (Funded by CIHR)

authors

  • Stokl, Andrew James
  • Safdar, Adeel
  • Hettinga, Bart P
  • Ogborn, Daniel I
  • Kujoth, Gregory C
  • Prolla, Tomas A
  • Tarnopolsky, Mark

publication date

  • April 2010