Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy.
To investigate the cause of skeletal muscle weakening during aging we examined the sequence of cellular changes in murine muscles. Satellite cells isolated from single muscle fibers terminally differentiate progressively less well with increasing age of donor. This change is detected before decline in satellite cell numbers and all histological changes examined here. In MSVski transgenic mice, which show type IIb fiber hypertrophy, initial muscle weakness is followed by muscle degeneration in the first year of life. This degeneration is accompanied by a spectrum of changes typical of normal muscle aging and a more marked decline in satellite cell differentiation efficiency. On a myoD-null genetic background, in which satellite cell differentiation is defective, the MSVski muscle phenotype is aggravated. This suggests that, on a wild-type genetic background, satellite cells are capable of repairing MSVski fibers and preserving muscle integrity in early life. We propose that decline in myogenic cell differentiation efficiency is an early event in aging-related loss of muscle function, both in normal aging and in some late-onset muscle degenerative conditions.
Chargé
Sophie B P
SB
Medical Research Council (MRC) Muscle and Cell Motility Unit, MRC Centre for Developmental Neurobiology, Guy's Campus, King's College London, London SE1 1UL, UK.
Brack
Andrew S
AS
Hughes
Simon M
SM
D000375:Aging / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology*; D066298:In Vitro Techniques; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D017570:MyoD Protein / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000473:pathology
D004268:DNA-Binding Proteins; D017570:MyoD Protein; D011518:Proto-Oncogene Proteins; C512653:Ski protein, mouse