title: Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function.
abstract: In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n = 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls (n = 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in cross-sectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men. Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems.
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Damien M
authors: DM
authors: Callahan
authors: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, Vermont.
authors: Timothy W
authors: TW
authors: Tourville
authors: Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont; and.
authors: Mark S
authors: MS
authors: Miller
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Sarah B
authors: SB
authors: Hackett
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Himani
authors: H
authors: Sharma
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Nicholas C
authors: NC
authors: Cruickshank
authors: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, Vermont.
authors: James R
authors: JR
authors: Slauterbeck
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Patrick D
authors: PD
authors: Savage
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont;
authors: Philip A
authors: PA
authors: Ades
authors: Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont; and.
authors: David W
authors: DW
authors: Maughan
authors: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, Vermont.
authors: Bruce D
authors: BD
authors: Beynnon
authors: Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont; Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont; and michael.toth@uvm.edu.
authors: Michael J
authors: MJ
authors: Toth
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015444:Exercise; D005260:Female; D015870:Gene Expression; D006801:Humans; D007717:Knee / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D012737:Sex Factors
chemical_list: D020033:Protein Isoforms; D018995:Myosin Heavy Chains
keywords: mitochondria; myosin; physical activity; ultrastructure