P38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice

Jennifer D. Bernet, Jason D. Doles, John K. Hall, Kathleen Kelly Tanaka, Thomas A. Carter, Bradley B. Olwin

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via alterations in fibroblast growth factor receptor-1, p38α and p38β mitogen-activated protein kinase signaling in satellite cells from aged mice. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveal potential therapeutic opportunities for the treatment of progressive muscle wasting.

Original languageEnglish (US)
Pages (from-to)265-271
Number of pages7
JournalNature Medicine
Volume20
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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