title: Activation of an adipogenic program in adult myoblasts with age.
abstract: 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/EBPalpha, and in the relative abundance of PPARgamma2 to PPARgamma1 mRNAs. Furthermore, PPARgamma 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 PPARgamma and C/EBPalpha, 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 beta-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.
authors.affiliation: Department of Geriatrics, Donald W. Reynolds Center on Aging, University of Arkansas for Medical Sciences, 629 South Elm Street, Little Rock, AR 72205, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Taylor-Jones
authors.forename: Robert E
authors.initials: RE
authors.lastname: McGehee
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
authors.forename: Beata
authors.initials: B
authors.lastname: Lecka-Czernik
authors.forename: David A
authors.initials: DA
authors.lastname: Lipschitz
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002352:Carrier Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D051153:Wnt Proteins
chemical_list: D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha; D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; C491119:WNT10B protein, human; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D008071:Lipoprotein Lipase