Examining Mechanisms of Altered Skeletal Muscle Cellular Passive Mechanics in the Context of Acute Fatigue and Age
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Date
2024-12-19
Authors
Privett, Grace
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Publisher
University of Oregon
Abstract
Skeletal muscle stiffness influences locomotor function and may predict soft-tissue injury risk. Recent literature suggests fatiguing exercise transiently reduces whole skeletal muscle stiffness, yet the underlying mechanisms remain unclear. Therefore, the purpose of this dissertation was to i) determine whether fatiguing exercise reduces cellular passive stress and Young’s Modulus in conjunction with altered phosphorylation of the sarcomere protein titin, ii) extend these measures to samples of composite tissue, and iii) assess whether aging mediates the effect of fatigue on skeletal muscle passive mechanics. Methods: 9 young and 8 older males and females completed unilateral fatiguing exercise followed by biopsy of the fatigued and non-fatigued Vastus Lateralis. In younger adults, passive stress and strain were compared in fatigued versus non-fatigued single fibers and titin phosphorylation was quantified via liquid chromatography mass spectrometry (LC-MS, Aim 1). Cellular measures were then translated to bundles of 12-14 fibers with intact extracellular matrix (ECM, Aim 2). Finally, cellular and tissue-level mechanical measures were compared in young versus older adults (Aim 3). Results: We observed that fatiguing exercise reduced passive stress and Young’s Modulus in myosin heavy chain (MHC) IIA and IIA/X fibers from young and older males, but not females. Titin phosphorylation was altered by fatiguing exercise, with no apparent sex-based differences. In-vitro treatments to phosphorylate or dephosphorylate titin did not support a direct link between titin phosphorylation and altered cellular passive mechanics. In bundles, fatiguing exercise only affected passive modulus in young females, and this fatigue-induced difference was at least partially due to titin. Aging did not affect cellular or bundle passive measures, nor did aging mediate the response to fatigue. Discussion: These data suggest that fatiguing exercise reduces cellular passive stress and modulus in muscle from older and younger males, in conjunction with altered titin phosphorylation. Furthermore, intracellular proteins appear to contribute to tissue mechanics, though their relative influence is unclear. Ultimately this study contributes to efforts aimed at understanding the chronic and acute mediators of skeletal muscle mechanics.
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Keywords
aging physiology, cellular mechanics, cellular stiffness, fatiguing exercise, skeletal muscle, titin