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Articles in PresS, published online ahead of print June 26, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00206.2002
Submitted on May 3, 2002
Accepted on June 19, 2002
1 Developmental Neurobiology, King's College London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: simon.hughes{at}kcl.ac.uk.
To investigate the cause of skeletal muscle weakening during aging we have examined the sequence of cellular changes in murine muscles. Satellite cells isolated from single muscle fibers terminally differentiate progressively less well with age of donor. This change is detected prior to decline in satellite cell numbers and all histological changes examined. 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, as well as a 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 wildtype 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.
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