An investigation of p53 in skeletal muscle aging

Scott M. Ebert, Jason M. Dierdorff, David K. Meyerholz, Steven A. Bullard, Asma Al-Zougbi, Austin D. DeLau, Kristin C. Tomcheck, Zachary P. Skopec, George R. Marcotte, Sue C. Bodine, Christopher M. Adams

Research output: Contribution to journalArticlepeer-review


Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53 may play a central, causative role in skeletal muscle aging, whereas other, apparently contradictory lines of evidence have suggested that p53 may be critical for normal skeletal muscle function. To help address these issues, we performed an aging study in male muscle-specific p53-knockout mice (p53 mKO mice), which have a lifelong absence of p53 expression in skeletal muscle fibers. We found that the absence of p53 expression in skeletal muscle fibers had no apparent deleterious or beneficial effects on skeletal muscle mass or function under basal conditions up to 6 mo of age, when mice are fully grown and exhibit peak muscle mass and function. Furthermore, at 22 and 25 mo of age, when age-related muscle weakness and atrophy are clearly evident in mice, p53 mKO mice demonstrated no improvement or worsening of skeletal muscle mass or function relative to littermate control mice. At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice. In light of these results, we conclude that p53 expression in skeletal muscle fibers has minimal if any direct, cell autonomous effect on basal or age-related changes in skeletal muscle mass and function up to at least 22 mo of age. NEW & NOTEWORTHY Previous studies implicated the transcriptional regulator p53 as a potential mediator of age-related skeletal muscle weakness and atrophy. We tested this hypothesis by investigating the effect of aging in muscle-specific p53-knockout mice. Our results strongly suggest that p53 activity within skeletal muscle fibers is not required for age-related skeletal muscle atrophy or weakness.

Original languageEnglish (US)
Pages (from-to)1075-1084
Number of pages10
JournalJournal of applied physiology
Issue number4
StatePublished - 2019


  • Aging
  • Muscle atrophy
  • P53
  • Sarcopenia
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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