Non-passaged muscle precursor cells from 32-month old rat skeletal muscle have delayed proliferation and differentiation

Cell Prolif. 2013 Feb;46(1):45-57. doi: 10.1111/cpr.12007. Epub 2012 Dec 21.

Abstract

Objectives: The systemic environment and satellite cell dysfunction have been proposed as important contributors in the development of sarcopenia and impaired skeletal muscle regrowth with ageing. In the present study, we investigated effects of serum age on proliferation of muscle precursor cells (MPCs) isolated from skeletal muscles of young and old rats.

Materials and methods: We examined proliferation and subsequent differentiation of non-passaged MPCs isolated from skeletal muscles of 1-, 3- and 32-month old rats over a 72-h time course, using a serum cross-over design.

Results and conclusions: We found no effect of serum age on MPC proliferation, but we did discover that MPCs isolated from skeletal muscle of 32-month old rats had delayed onset of, and exit from proliferation, compared to MPCs isolated from skeletal muscle of 1-month old rats. Delayed proliferation of MPCs from 32-month old rats was associated with delayed p38 MAPK phosphorylation, and MyoD and p21(Cip1) protein expression. We also demonstrate that MPCs from 32-month old rats exhibited lower levels of muscle creatine kinase mRNA compared to 1-month old rats, but elevated levels of myogenin mRNA, when stimulated to differentiate after 36 h proliferation. These findings suggest that delayed entry and exit of the cell cycle observed in MPCs from 32-month old rats may compromise their ability to respond to differentiation stimuli and subsequently impair myogenic potential of 32-month old skeletal muscle, in this model.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Creatine Kinase / genetics
  • Creatine Kinase / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Male
  • Muscle, Skeletal / cytology*
  • MyoD Protein / metabolism
  • Myoblasts / cytology*
  • Myoblasts / enzymology
  • Myoblasts / metabolism
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • MyoD Protein
  • RNA, Messenger
  • p38 Mitogen-Activated Protein Kinases
  • Creatine Kinase