title: The central role of muscle stem cells in regenerative failure with aging.
abstract: Skeletal muscle mass, function, and repair capacity all progressively decline with aging, restricting mobility, voluntary function, and quality of life. Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues. In adult tissues, MuSCs are retained in a quiescent state until they are primed to regenerate damaged muscle through cycles of self-renewal divisions. With aging, muscle tissue homeostasis is progressively disrupted and the ability of MuSCs to repair injured muscle markedly declines. Until recently, this decline has been largely attributed to extrinsic age-related alterations in the microenvironment to which MuSCs are exposed. However, as highlighted in this Perspective, recent reports show that MuSCs also progressively undergo cell-intrinsic alterations that profoundly affect stem cell regenerative function with aging. A more comprehensive understanding of the interplay of stem cell-intrinsic and extrinsic factors will set the stage for improving cell therapies capable of restoring tissue homeostasis and enhancing muscle repair in the aged.
authors.affiliation: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Blau
authors.affiliation: Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Cosgrove
authors.affiliation: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Andrew T V
authors.initials: AT
authors.lastname: Ho
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D016764:Cell Polarity; D016922:Cellular Senescence; D055412:Growth Differentiation Factors / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D048051:p38 Mitogen-Activated Protein Kinases