title: Age-related slowing of myosin actin cross-bridge kinetics is sex specific and predicts decrements in whole skeletal muscle performance in humans.
abstract: We hypothesize that age-related skeletal muscle dysfunction and physical disability may be partially explained by alterations in the function of the myosin molecule. To test this hypothesis, skeletal muscle function at the whole muscle, single fiber, and molecular levels was measured in young (21-35 yr) and older (65-75 yr) male and female volunteers with similar physical activity levels. After adjusting for muscle size, older adults had similar knee extensor isometric torque values compared with young, but had lower isokinetic power, most notably in women. At the single-fiber and molecular levels, aging was associated with increased isometric tension, slowed myosin actin cross-bridge kinetics (longer myosin attachment times and reduced rates of myosin force production), greater myofilament lattice stiffness, and reduced phosphorylation of the fast myosin regulatory light chain; however, the age effect was driven primarily by women (i.e., age-by-sex interaction effects). In myosin heavy chain IIA fibers, single-fiber isometric tension and molecular level mechanical and kinetic indexes were correlated with whole muscle isokinetic power output. Collectively, considering that contractile dysfunction scales up through various anatomical levels, our results suggest a potential sex-specific molecular mechanism, reduced cross-bridge kinetics, contributes to the reduced physical capacity with aging in women. Thus these results support our hypothesis that age-related alterations in the myosin molecule contribute to skeletal muscle dysfunction and physical disability and indicate that this effect is stronger in women.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Burlington, Vermont;
authors.forename: Mark S
authors.initials: MS
authors.lastname: Miller
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Bedrin
authors.forename: Damien M
authors.initials: DM
authors.lastname: Callahan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Previs
authors.forename: Mark E
authors.initials: ME
authors.lastname: Jennings
authors.forename: Philip A
authors.initials: PA
authors.lastname: Ades
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toth
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D007700:Kinetics; D007717:Knee / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D055815:Young Adult
chemical_list: D000199:Actins; D018995:Myosin Heavy Chains
keywords: aging; mechanical properties; muscle fiber