title: Muscle disuse alters skeletal muscle contractile function at the molecular and cellular levels in older adult humans in a sex-specific manner.
abstract: Physical inactivity that accompanies ageing and disease may hasten disability by reducing skeletal muscle contractility. To characterize skeletal muscle functional adaptations to muscle disuse, we compared contractile performance at the molecular, cellular and whole‐muscle levels in healthy active older men and women (n = 15) and inactive older men and women with advanced‐stage, symptomatic knee osteoarthritis (OA) (n = 16). OA patients showed reduced (P < 0.01) knee extensor function. At the cellular level, single muscle fibre force production was reduced in OA patients in myosin heavy chain (MHC) I and IIA fibres (both P < 0.05) and differences in IIA fibres persisted after adjustments for fibre cross‐sectional area (P < 0.05). Although no group differences in contractile velocity or power output were found for any fibre type, sex was found to modify the effect of OA, with a reduction in MHC IIA power output and a trend towards reduced shortening velocity in women, but increases in both variables in men (P < 0.05 and P = 0.07, respectively). At the molecular level, these adaptations in MHC IIA fibre function were explained by sex‐specific differences (P ≤ 0.05) in myosin–actin cross‐bridge kinetics. Additionally, cross‐bridge kinetics were slowed in MHC I fibres in OA patients (P < 0.01), attributable entirely to reductions in women with knee OA (P < 0.05), a phenotype that could be reproduced in vitro by chemical modification of protein thiol residues. Our results identify molecular and cellular functional adaptations in skeletal muscle that may contribute to reduced physical function with knee OA‐associated muscle disuse, with sex‐specific differences that may explain a greater disposition towards disability in women.
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Damien M
authors.initials: DM
authors.lastname: Callahan
authors.affiliation: Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Miller
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Sweeny
authors.affiliation: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Tourville
authors.affiliation: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Slauterbeck
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Savage
authors.affiliation: Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Maugan
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Ades
authors.affiliation: Department of Orthopaedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Beynnon
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, VT, USA michael.toth@uvm.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toth
mesh_terms: D000199:Actins / Q000378:metabolism; D000222:Adaptation, Physiological; D000368:Aged; D000375:Aging / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007717:Knee / Q000254:growth & development / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D024461:Myosin Type I / Q000378:metabolism; D010003:Osteoarthritis / Q000503:physiopathology*; D012737:Sex Factors
chemical_list: D000199:Actins; D024461:Myosin Type I