Skeletal muscle aging, cellular senescence, and senotherapeutics: Current knowledge and future directions

Davis A. Englund, Xu Zhang, Zaira Aversa, Nathan K. LeBrasseur

Research output: Contribution to journalArticlepeer-review


Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive phenotype, characterized by profound chromatin alterations and a robust senescence-associated secretory phenotype (SASP) that exerts negative effects on tissue health, both locally and systemically. In preclinical models, pharmacological agents that eliminate senescent cells (senotherapeutics) restore health and youthful properties in multiple tissues. To date, however, very little is understood about the vulnerability of terminally-differentiated skeletal muscle fibers and the resident mononuclear cells that populate the interstitial microenvironment of skeletal muscle to senescence, and their contribution to the onset and progression of skeletal muscle loss and dysfunction with aging. Scientific advances in these areas have the potential to highlight new therapeutic approaches to optimize late-life muscle health. To this end, this review highlights the current evidence and the key questions that need to be addressed to advance the field's understanding of cellular senescence as a mediator of skeletal muscle aging and the potential for emerging senescent cell-targeting therapies to counter age-related deficits in muscle mass, strength, and function.

Original languageEnglish (US)
Article number111595
JournalMechanisms of Ageing and Development
StatePublished - Dec 2021


  • Fibroadipogenic progenitor cells
  • Muscle fiber
  • Sarcopenia
  • Satellite cells
  • Senescence-associated secretory phenotype
  • Senolytics

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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