Title | Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Lee JD, Fry CS, Mula J, Kirby TJ, Jackson JR, Liu F, Yang L, Dupont-Versteegden EE, McCarthy JJ, Peterson CA |
Journal | J Gerontol A Biol Sci Med Sci |
Volume | 71 |
Issue | 4 |
Pagination | 461-7 |
Date Published | 2016 Apr |
ISSN | 1758-535X |
Keywords | Adaptation, Physiological, Animals, Cell Proliferation, Cellular Microenvironment, Disease Models, Animal, Extracellular Matrix, Hypertrophy, Immunoenzyme Techniques, Mice, Mice, Transgenic, Muscle Fibers, Skeletal, Random Allocation, Sarcopenia, Satellite Cells, Skeletal Muscle, Stress, Mechanical, Tamoxifen |
Abstract | 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. |
DOI | 10.1093/gerona/glv033 |
Alternate Journal | J. Gerontol. A Biol. Sci. Med. Sci. |
PubMed ID | 25878030 |
PubMed Central ID | PMC5175449 |
Grant List | R21 AG034453 / AG / NIA NIH HHS / United States AR60701 / AR / NIAMS NIH HHS / United States AG34453 / AG / NIA NIH HHS / United States UL1TR000117 / TR / NCATS NIH HHS / United States R01 AR060701 / AR / NIAMS NIH HHS / United States AR065337 / AR / NIAMS NIH HHS / United States |