Abstract
We report an age-dependent increase in nonimmunohematopoietic cells (CD45neg) in regenerating muscle characterized by high stem-cell antigen (Sca-1) expression. In aged regenerating muscle, only 14% of these CD45negSca-1pos cells express MyoD, whereas 82% of CD45negSca-1pos cells are MyoDpos in young adult muscle. In vitro, CD45negMyoDnegSca-1pos cells overexpress fibrosis-promoting genes, potentially controlled by Wnt2. The cells are proliferative, nonmyogenic, and nonadipogenic, and arise in clonally derived myoblast cultures from aged mice. MyoDneg Sca-1pos nonmyogenic cells also emerge in C2C12 myoblast cultures at late passage. Both in vitro and in vivo studies suggest that MyoDnegSca-1pos cells from aged muscle are more susceptible to apoptosis than myoblasts, which may contribute to depletion of the satellite cell pool. Thus, with age, a subset of myoblasts takes on an altered phenotype, which is marked by high Sca-1 expression. These cells do not participate in muscle regeneration, and instead may contribute to muscle fibrosis in aged muscle.
Original language | English |
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Pages (from-to) | 566-579 |
Number of pages | 14 |
Journal | Journals of Gerontology - Series A Biological Sciences and Medical Sciences |
Volume | 63 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2008 |
Keywords
- Aging
- Fibrosis
- Muscle stem cells
- Sca-1
- Skeletal muscle regeneration
ASJC Scopus subject areas
- Aging
- Geriatrics and Gerontology