Age affects myosin relaxation states in skeletal muscle fibers of female but not male mice

Lien A. Phung, Sira M. Karvinen, Brett A. Colson, David D. Thomas, Dawn A. Lowe

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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 20/30-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.

Original languageEnglish (US)
Article numbere0199062
JournalPloS one
Issue number9
StatePublished - Sep 2018

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (NIH) grants to DAL (R01 AG031743), and DDT (R01 AR032961, R37 AG26160). LAP was supported by NIH Medical Scientist Training Program grant T32 GM008244, NIH T32 AG29796, and F30 AG057108.

Publisher Copyright:
© 2018 Phung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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