Title | Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Fry CS, Lee JD, Mula J, Kirby TJ, Jackson JR, Liu F, Yang L, Mendias CL, Dupont-Versteegden EE, McCarthy JJ, Peterson CA |
Journal | Nat Med |
Volume | 21 |
Issue | 1 |
Pagination | 76-80 |
Date Published | 2015 Jan |
ISSN | 1546-170X |
Keywords | Aging, Animals, Humans, Mice, Muscle, Skeletal, Regeneration, Sarcopenia, Satellite Cells, Skeletal Muscle |
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. |
DOI | 10.1038/nm.3710 |
Alternate Journal | Nat. Med. |
PubMed ID | 25501907 |
PubMed Central ID | PMC4289085 |
Grant List | UL1 TR000117 / TR / NCATS NIH HHS / United States R21 AG034453 / AG / NIA NIH HHS / United States AR60701 / AR / NIAMS NIH HHS / United States AG34453 / AG / NIA NIH HHS / United States R21 AG043721 / AG / NIA NIH HHS / United States UL1TR000117 / TR / NCATS NIH HHS / United States AG043721 / AG / NIA NIH HHS / United States R01 AR060701 / AR / NIAMS NIH HHS / United States AR065337 / AR / NIAMS NIH HHS / United States R01 AR065479 / AR / NIAMS NIH HHS / United States K12 DE023574 / DE / NIDCR NIH HHS / United States |