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RESEARCH PRODUCT
Age affects myosin relaxation states in skeletal muscle fibers of female but not male mice
Lien A. PhungBrett A. ColsonDavid D. ThomasDawn A. LoweSira Karvinensubject
Adenosine TriphosphataseMale0301 basic medicineAgingMuscle PhysiologyPhysiologyMuscle RelaxationATPaseMuscle Fibers Skeletallcsh:MedicineMale miceSkeletal Muscle FibersBiochemistrymyosinsMiceMyosin headContractile Proteins0302 clinical medicineAnimal Cellsskeletal muscle fibresMyosinMedicine and Health SciencesgenderLipid HormonesPost-Translational ModificationPhosphorylationlcsh:Scienceta315Musculoskeletal SystemSex Characteristics0303 health sciencesMultidisciplinaryEstradiolRelaxation (psychology)biologyChemistryMusclesanimal experimentsEnzymesmedicine.anatomical_structurePhosphorylationFemaleCellular TypesAnatomyResearch ArticleMuscle ContractionSex characteristicsmedicine.medical_specialtyMotor ProteinssukupuolierotActin MotorseläinkokeetMuscle Fibersmyosiinitsukupuoli03 medical and health sciencesAtrophyMolecular MotorsInternal medicinemedicineAnimalslihassolut030304 developmental biology030102 biochemistry & molecular biologylcsh:RPhosphatasesBiology and Life SciencesProteinsSkeletal muscleCell BiologySkeletal Muscle Fibersmedicine.diseaseHormonesCytoskeletal Proteins030104 developmental biologyEndocrinologySkeletal MusclesageEnzymologybiology.proteinlcsh:QSteady state (chemistry)ikä030217 neurology & neurosurgerydescription
The recent discovery that myosin has two distinct states in relaxed muscle–disordered relaxed (DRX) and super-relaxed (SRX)–provides another factor to consider in our fundamental understanding of the aging mechanism in skeletal muscle, since myosin is thought to be a potential contributor to dynapenia (age-associated loss of muscle strength independent of atrophy). The primary goal of this study was to determine the effects of age on DRX and SRX states and to examine their sex specificity. We have used quantitative fluorescence microscopy of the fluorescent nucleotide analog 2′/3′-O-(N-methylanthraniloyl) ATP (mantATP) to measure single-nucleotide turnover kinetics of myosin in skinned skeletal muscle fibers under relaxing conditions. We examined changes in DRX and SRX in response to the natural aging process by measuring the turnover of mantATP in skinned fibers isolated from psoas muscle of adult young (3–4 months old) and aged (26–28 months old) C57BL/6 female and male mice. Fluorescence decays were fitted to a multi-exponential decay function to determine both the time constants and mole fractions of fast and slow turnover populations, and significance was analyzed by a t-test. We found that in females, both the DRX and SRX lifetimes of myosin ATP turnover at steady state were shorter in aged muscle fibers compared to young muscle fibers (p ≤ 0.033). However, there was no significant difference in relaxation lifetime of either DRX (p = 0.202) or SRX (p = 0.804) between young and aged male mice. No significant effects were measured on the mole fractions (populations) of these states, as a function of sex or age (females, p = 0.100; males, p = 0.929). The effect of age on the order of myosin heads at rest and their ATPase function is sex specific, affecting only females. These findings provide new insight into the molecular factors and mechanisms that contribute to aging muscle dysfunction in a sex-specific manner. peerReviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-06-01 |