title: p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice.
abstract: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via alterations in fibroblast growth factor receptor-1, p38α and p38β mitogen-activated protein kinase signaling in satellite cells from aged mice. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveal potential therapeutic opportunities for the treatment of progressive muscle wasting.
authors: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors: Jennifer D
authors: JD
authors: Bernet
authors: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors: Jason D
authors: JD
authors: Doles
authors: 1] Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA. [2].
authors: John K
authors: JK
authors: Hall
authors: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors: Kathleen
authors: K
authors: Kelly Tanaka
authors: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors: Thomas A
authors: TA
authors: Carter
authors: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors: Bradley B
authors: BB
authors: Olwin
mesh_terms: D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D017690:Cell Transplantation; D004777:Environment; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D008024:Ligands; D016220:Fibroblast Growth Factor 1; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14