title: Electron paramagnetic resonance reveals age-related myosin structural changes in rat skeletal muscle fibers.
abstract: We tested the hypothesis that low specific tension (force/cross-sectional area) in skeletal muscle from aged animals results from structural changes in myosin that occur with aging. Permeabilized semimembranosus fibers from young adult and aged rats were spin labeled site specifically at myosin SH1 (Cys-707). Electron paramagnetic resonance (EPR) was then used to resolve and quantify the structural states of the myosin head to determine the fraction of myosin heads in the strong-binding (force generating) structural state during maximal isometric contraction. Fibers from aged rats generated 27 +/- 0.8% less specific tension than fibers from younger rats (P < 0.001). EPR spectral analyses showed that, during contraction, 31.6 +/- 2.1% of myosin heads were in the strong-binding structural state in fibers from young adult animals but only 22.1 +/- 1.3% of myosin heads in fibers from aged animals were in that state (P = 0.004). Biochemical assays indicated that the age-related change in myosin structure could be due to protein oxidation, as indicated by a decrease in the number of free cysteine residues. We conclude that myosin structural changes can provide a molecular explanation for age-related decline in skeletal muscle force generation.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, Minnesota 55455, USA. dl@ddt.biochem.umn.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Lowe
authors.forename: J T
authors.initials: JT
authors.lastname: Surek
authors.forename: D D
authors.initials: DD
authors.lastname: Thomas
authors.forename: L V
authors.initials: LV
authors.lastname: Thompson
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D006824:Hybridization, Genetic; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009218:Myosins / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D009218:Myosins