title: Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance.
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.
authors: Department of Rehabilitation Sciences, College of Health Sciences and Center for Muscle Biology, University of Kentucky, Lexington. Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor.
authors: Jonah D
authors: JD
authors: Lee
authors: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston.
authors: Christopher S
authors: CS
authors: Fry
authors: Department of Rehabilitation Sciences, College of Health Sciences and Center for Muscle Biology, University of Kentucky, Lexington.
authors: Jyothi
authors: J
authors: Mula
authors: Center for Muscle Biology, University of Kentucky, Lexington. Department of Physiology, College of Medicine, University of Kentucky, Lexington.
authors: Tyler J
authors: TJ
authors: Kirby
authors: Department of Rehabilitation Sciences, College of Health Sciences and Center for Muscle Biology, University of Kentucky, Lexington.
authors: Janna R
authors: JR
authors: Jackson
authors: Department of Biomedical Engineering, University of Florida, Gainesville.
authors: Fujun
authors: F
authors: Liu
authors: Department of Biomedical Engineering, University of Florida, Gainesville.
authors: Lin
authors: L
authors: Yang
authors: Department of Rehabilitation Sciences, College of Health Sciences and Center for Muscle Biology, University of Kentucky, Lexington.
authors: Esther E
authors: EE
authors: Dupont-Versteegden
authors: Center for Muscle Biology, University of Kentucky, Lexington. Department of Physiology, College of Medicine, University of Kentucky, Lexington.
authors: John J
authors: JJ
authors: McCarthy
authors: Department of Rehabilitation Sciences, College of Health Sciences and Center for Muscle Biology, University of Kentucky, Lexington. Department of Physiology, College of Medicine, University of Kentucky, Lexington. cpete4@uky.edu.
authors: Charlotte A
authors: CA
authors: Peterson
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D006984:Hypertrophy / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D011897:Random Allocation; D055948:Sarcopenia / Q000503:physiopathology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D013314:Stress, Mechanical; D013629:Tamoxifen
chemical_list: D013629:Tamoxifen
keywords: Fibrosis.; Muscle; Regeneration; Sarcopenia; Satellite; cells; overload