Format

Send to

Choose Destination
Aging Cell. 2016 Dec;15(6):1132-1139. doi: 10.1111/acel.12520. Epub 2016 Aug 25.

Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age.

Author information

1
Centre for Prions and Protein Folding Diseases, Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
2
Division of Geriatrics, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
3
Centre for Prions and Protein Folding Diseases, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.

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.

KEYWORDS:

aging; mitochondrial DNA deletion mutation; muscle; sarcopenia

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center