title: Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia.
abstract: A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis.
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Jonah D
authors.initials: JD
authors.lastname: Lee
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Mula
authors.affiliation: 1] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. [2] Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Kirby
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Janna R
authors.initials: JR
authors.lastname: Jackson
authors.affiliation: 1] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. [2] Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Fujun
authors.initials: F
authors.lastname: Liu
authors.affiliation: 1] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. [2] Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Esther E
authors.initials: EE
authors.lastname: Dupont-Versteegden
authors.affiliation: 1] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. [2] Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: McCarthy
authors.affiliation: 1] Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA. [2] Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. [3] Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000254:growth & development / Q000503:physiopathology*; D012038:Regeneration / Q000235:genetics; D055948:Sarcopenia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology*