Increased aging in primary muscle cultures of sporadic inclusion-body myositis

Neurobiol Aging. 2010 Jul;31(7):1205-14. doi: 10.1016/j.neurobiolaging.2008.08.011. Epub 2008 Sep 26.

Abstract

Ageing is thought to participate to the pathogenesis of sporadic inclusion-body myositis (s-IBM). Although the regenerative potential of s-IBM muscle is reduced in vivo, age-related abnormalities of satellite cells possibly accounting for the decline of muscle repair have not been demonstrated. Here we show that proliferation rate and clonogenicity of s-IBM myoblasts are significantly lower and doubling time is longer than normal age-matched controls, indicating that proliferative capacity of s-IBM muscles becomes exhausted earlier. Telomere shortening is detected in s-IBM cells suggesting premature senescence. Differently from controls, s-IBM myoblasts show increased active beta-catenin mainly localized within myonuclei, indicating active Wnt stimulation. After many rounds of muscle growth, only s-IBM myoblasts accumulate congophilic inclusions and immunoreactive Abeta(1-40) deposits. Therefore, s-IBM myoblasts seem to have a constitutively impaired regenerative capacity and the intrinsic property, upon sufficient aging in vitro, to accumulate Abeta. Our results might be valuable in understanding molecular mechanisms associated with muscle aging underlying the defective regeneration of s-IBM muscle and provide new clues for future therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Female
  • Humans
  • Inclusion Bodies / pathology*
  • Inclusion Bodies / physiology
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology*
  • Myoblasts / pathology*
  • Myositis, Inclusion Body / diagnosis
  • Myositis, Inclusion Body / pathology*
  • Myositis, Inclusion Body / physiopathology*
  • Satellite Cells, Skeletal Muscle / pathology
  • Satellite Cells, Skeletal Muscle / physiology
  • Telomere / pathology
  • Telomere / physiology