Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia

Christopher Fry, Jonah D. Lee, Jyothi Mula, Tyler J. Kirby, Janna R. Jackson, Fujun Liu, Lin Yang, Christopher L. Mendias, Esther E. Dupont-Versteegden, John J. McCarthy, Charlotte A. Peterson

Research output: Contribution to journalArticle

164 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)76-80
Number of pages5
JournalNature Medicine
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Sarcopenia
Muscle
Satellites
Muscles
Aging of materials
Fibrosis
Muscle Strength
Geriatrics
Muscle Cells
Regeneration
Young Adult
Skeletal Muscle
Stem Cells
Maintenance
Stem cells
Animals
Fibers
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. / Fry, Christopher; Lee, Jonah D.; Mula, Jyothi; Kirby, Tyler J.; Jackson, Janna R.; Liu, Fujun; Yang, Lin; Mendias, Christopher L.; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

In: Nature Medicine, Vol. 21, No. 1, 01.01.2015, p. 76-80.

Research output: Contribution to journalArticle

Fry, C, Lee, JD, Mula, J, Kirby, TJ, Jackson, JR, Liu, F, Yang, L, Mendias, CL, Dupont-Versteegden, EE, McCarthy, JJ & Peterson, CA 2015, 'Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia', Nature Medicine, vol. 21, no. 1, pp. 76-80. https://doi.org/10.1038/nm.3710
Fry, Christopher ; Lee, Jonah D. ; Mula, Jyothi ; Kirby, Tyler J. ; Jackson, Janna R. ; Liu, Fujun ; Yang, Lin ; Mendias, Christopher L. ; Dupont-Versteegden, Esther E. ; McCarthy, John J. ; Peterson, Charlotte A. / Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. In: Nature Medicine. 2015 ; Vol. 21, No. 1. pp. 76-80.
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