Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance

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

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35 Citations (Scopus)


Although sarcopenia, age-associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7(CreER)-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle-treated mice mounted a regenerative response, not apparent in tamoxifen-treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber-type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.

Original languageEnglish
Pages (from-to)461-7
Number of pages7
JournalThe Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Issue number4
Publication statusPublished - Apr 2016


  • Adaptation, Physiological
  • Animals
  • Cell Proliferation
  • Cellular Microenvironment
  • Disease Models, Animal
  • Extracellular Matrix/physiology
  • Hypertrophy/physiopathology
  • Immunoenzyme Techniques
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Skeletal/physiology
  • Random Allocation
  • Sarcopenia/physiopathology
  • Satellite Cells, Skeletal Muscle/cytology
  • Stress, Mechanical
  • Tamoxifen

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