Metabolomic analysis of exercise effects in the POLG mitochondrial DNA mutator mouse brain Academic Article uri icon


MeSH Major

  • Aging
  • Brain
  • DNA, Mitochondrial
  • DNA-Directed DNA Polymerase
  • Mutation
  • Neurotransmitter Agents


  • Mitochondrial DNA (mtDNA) mutator mice express a mutated form of mtDNA polymerase gamma that results an accelerated accumulation of somatic mtDNA mutations in association with a premature aging phenotype. An exploratory metabolomic analysis of cortical metabolites in sedentary and exercised mtDNA mutator mice and wild-type littermate controls at 9-10¬†months of age was performed. Pathway analysis revealed deficits in the neurotransmitters acetylcholine, glutamate, and aspartate that were ameliorated by exercise. Nicotinamide adenine dinucleotide (NAD) depletion and evidence of increased poly(adenosine¬†diphosphate-ribose) polymerase 1 (PARP1)activity were apparent in sedentary mtDNA mutator mouse cortex, along with deficits in carnitine metabolites and an upregulated antioxidant response that largely normalized with exercise. These data highlight specific pathways that are altered in the brain in association with an accelerated age-related accumulation of somatic mtDNA mutations. These results may have relevance to age-related neurodegenerative diseases associated with mitochondrial dysfunction, such as Alzheimer's disease and Parkinson's disease and provide insights into potential mechanisms of beneficial effects of exercise on brain function.

publication date

  • January 2015



  • Academic Article



  • eng

PubMed Central ID

  • PMC4609600

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2015.07.020

PubMed ID

  • 26294258

Additional Document Info

start page

  • 2972

end page

  • 83


  • 36


  • 11