Preservation of satellite cell number and regenerative potential with age reveals locomotory muscle bias

Robert W Arpke, Ahmed S. Shams, Brittany C. Collins, Alexie A. Larson, Nguyen Lu, Dawn A. Lowe, Michael Kyba

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Although muscle regenerative capacity declines with age, the extent to which this is due to satellite cell-intrinsic changes vs. environmental changes has been controversial. The majority of aging studies have investigated hindlimb locomotory muscles, principally the tibialis anterior, in caged sedentary mice, where those muscles are abnormally under-exercised. Methods: We analyze satellite cell numbers in 8 muscle groups representing locomotory and non-locomotory muscles in young and 2-year-old mice and perform transplantation assays of low numbers of hind limb satellite cells from young and old mice. Results: We find that satellite cell density does not decline significantly by 2 years of age in most muscles, and one muscle, the masseter, shows a modest but statistically significant increase in satellite cell density with age. The tibialis anterior and extensor digitorum longus were clear exceptions, showing significant declines. We quantify self-renewal using a transplantation assay. Dose dilution revealed significant non-linearity in self-renewal above a very low threshold, suggestive of competition between satellite cells for space within the pool. Assaying within the linear range, i.e., transplanting fewer than 1000 cells, revealed no evidence of decline in cell-autonomous self-renewal or regenerative potential of 2-year-old murine satellite cells. Conclusion: These data demonstrate the value of comparative muscle analysis as opposed to overreliance on locomotory muscles, which are not used physiologically in aging sedentary mice, and suggest that self-renewal impairment with age is precipitously acquired at the geriatric stage, rather than being gradual over time, as previously thought.

Original languageEnglish (US)
Article number22
JournalSkeletal muscle
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This study was funded by the Muscular Dystrophy Association (MDA351022) and the NIH/National Institute on Aging (R21 AG034370, R01 AG031743, R01 AG062899) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR055685). RWA and BCC were supported by the Minnesota Muscle Training Grant, NIH T32 AR007612).

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Regeneration
  • Satellite cells
  • Transplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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