Myoblasts isolated from mouse hindlimb skeletal muscle demonstrated increased adipogenic potential as a function of age. Whereas myoblasts from 8-month-old adult mice did not significantly accumulate terminal markers of adipogenesis regardless of culture conditions, myoblasts from 23-month-old mice accumulated fat and expressed genes characteristic of differentiated adipocytes, such as the fatty acid binding protein aP2. This change in differentiation potential was associated with a change in the abundance of the mRNA encoding the transcription factor C/EBPα, and in the relative abundance of PPARγ2 to PPARγ1 mRNAs. Furthermore, PPARγ activity appeared to be regulated at the level of phosphorylation, being more highly phosphorylated in myoblasts isolated from younger animals. Although adipogenic gene expression in myoblasts from aged animals was activated, presumably in response to PPARγ and C/EBPα, unexpectedly, myogenic gene expression was not effectively repressed. The Wnt signaling pathway may also alter differentiation potential in muscle with age. Wnt-10b mRNA was more abundantly expressed in muscle tissue and cultured myoblasts from adult compared with aged mice, resulting in stabilization of cytosolic β-catenin, that may potentially contribute to inhibition of adipogenic gene expression in adult myoblasts. The changes reported here, together with those reported in bone marrow stroma with age, suggest that a default program may be activated in mesenchymal cells with increasing age resulting in a more adipogenic-like phenotype. Whether this change in differentiation potential contributes to the increased adiposity in muscle with age remains to be determined.
|Number of pages||13|
|Journal||Mechanisms of Ageing and Development|
|State||Published - Mar 31 2002|
Bibliographical noteFunding Information:
We thank Elena Moerman for excellent technical assistance and Dr Edward D. Bearden for statistical analysis. This work was supported by grants to C.A. Peterson from the National Institutes on Aging (AG00724 and AG13009), to R.E.M. from the National Cancer Institute (CA78845) and to T.A. Rando from the Department of Veterans Affairs and the American Federation for Aging Research.
- Adipogenic differentiation
- Myogenic differentiation
- Skeletal muscle
ASJC Scopus subject areas
- Developmental Biology