Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise

Exp Gerontol. 2010 Feb;45(2):138-48. doi: 10.1016/j.exger.2009.11.002. Epub 2009 Nov 10.


Sarcopenia, loss of muscle mass and function, is a common feature of aging. Oxidative damage and apoptosis are likely underlying factors. Autophagy, a process for the degradation of cellular constituents, may be a mechanism to combat cell damage and death. We investigated the effect of age on autophagy and apoptosis in plantaris muscle of male Fischer 344 rats that were either fed ad libitum, or mild, life-long calorie restricted (CR) alone or combined with life-long voluntary exercise. Upstream autophagy-regulatory proteins were either upregulated with age (Beclin-1) or unchanged (Atg7 and 9). LC3 gene and protein expression pattern as well as LAMP-2 gene expression, both downstream regulators of autophagy, however, suggested an age-related decline in autophagic degradation. Atg protein expression and LC3 and LAMP-2 gene expression were improved in CR rats with or without exercise. The age-related increase in oxidative damage and apoptosis were attenuated by the treatments. Both, oxidative damage and apoptosis correlated negatively with autophagy. We conclude that mild CR attenuates the age-related impairment of autophagy in rodent skeletal muscle, which might be one of the mechanisms by which CR attenuates age-related cellular damage and cell death in skeletal muscle in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / pathology*
  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / physiology
  • Beclin-1
  • Body Weight
  • Caloric Restriction*
  • Gene Expression / physiology
  • Life Style
  • Linear Models
  • Lysosomal-Associated Membrane Protein 2 / genetics
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Organ Size
  • Oxidative Stress / physiology
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Inbred F344
  • Sarcopenia / pathology*
  • Sarcopenia / prevention & control


  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, rat
  • LC3 protein, rat
  • Lysosomal-Associated Membrane Protein 2
  • Microtubule-Associated Proteins