title: Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age.
abstract: With age, somatically derived mitochondrial DNA (mtDNA) deletion mutations arise in many tissues and species. In skeletal muscle, deletion mutations clonally accumulate along the length of individual fibers. At high intrafiber abundances, these mutations disrupt individual cell respiration and are linked to the activation of apoptosis, intrafiber atrophy, breakage, and necrosis, contributing to fiber loss. This sequence of molecular and cellular events suggests a putative mechanism for the permanent loss of muscle fibers with age. To test whether mtDNA deletion mutation accumulation is a significant contributor to the fiber loss observed in aging muscle, we pharmacologically induced deletion mutation accumulation. We observed a 1200% increase in mtDNA deletion mutation-containing electron transport chain-deficient muscle fibers, an 18% decrease in muscle fiber number and 22% worsening of muscle mass loss. These data affirm the hypothesized role for mtDNA deletion mutation in the etiology of muscle fiber loss at old age.
authors: Centre for Prions and Protein Folding Diseases, Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
authors: Allen
authors: A
authors: Herbst
authors: Division of Geriatrics, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: Jonathan
authors: J
authors: Wanagat
authors: Centre for Prions and Protein Folding Diseases, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
authors: Nashwa
authors: N
authors: Cheema
authors: Division of Geriatrics, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors: Kevin
authors: K
authors: Widjaja
authors: Centre for Prions and Protein Folding Diseases, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
authors: Debbie
authors: D
authors: McKenzie
authors: Centre for Prions and Protein Folding Diseases, Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
authors: Judd M
authors: JM
authors: Aiken
keywords: aging; mitochondrial DNA deletion mutation; muscle; sarcopenia