Biology subjects

Ricci, A. W.

Publications and source records attributed to Ricci, A. W..

3 recordsLinked to original sources

bioRxiv2026

Sex-specific effects of fatiguing exercise on skeletal muscle passive mechanics are preserved in aging

Skeletal muscle function is central to the preservation of functional mobility. Given global shifts to an increasingly aged population, it is paramount that researchers and clinicians better understand the effectors of age-related functional decline. Muscle fatiguability acutely modifies skeletal muscle mechanics in ways that may affect joint stability. We have previously reported sex-specific reductions in cellular passive stress and modulus with fatigue in young males, but not females. Here, we assess whether older adults, who are more susceptible to fatigue during dynamic contractions, exhibit changes to cellular passive mechanics following fatiguing exercise. Muscle tissue biopsies were collected from 11 young and 11 older adults to measure passive stress and Youngs Modulus at the single fiber and bundle level. Biopsy samples were acquired from rested muscle and immediately following intermittent maximal contractions to task failure. Fatigue was associated with persistent reduction in elastic modulus that was specific to male participants, regardless of age. In muscle fiber bundles, containing both myofibrillar proteins and the extracellular matrix, fatigue-induced changes in modulus were largely negated, with the only significant change observed in young females, who demonstrated enhanced modulus with fatigue. Taken together our findings suggest a preservation of sex-based differences in the acute response to fatigue across the adult lifespan when measured at the myofilament level. However, further research is needed to understand how and whether these findings translate to the whole tissue level. New and noteworthyAcute modifications to muscle tissue mechanics are poorly understood but may have important impacts on functional outcomes in at-risk populations. Our findings suggest myocellular mechanics respond to acute fatigue stress in a sex specific manner that persists across the lifespan.

physiology↗

bioRxiv2024

Chronic and Acute Mediators of Passive Viscoelasticity in Human Skeletal Muscle Fibers

Cellular viscoelastic modulus in skeletal muscle tissue responds dynamically to chronic stressors, such as age and exercise. Passive tissue mechanics may also be sensitive to acute stimuli such as mechanical loading and/or activation-induced muscle fatigue. These insights are largely derived from preclinical studies of age and acute muscle activation. Therefore, we sought to understand the relative responsiveness of muscle cellular passive mechanics to chronic (resistance training) and acute (muscle fatigue) stressors in healthy young males and females categorized as "resistance trained" or "untrained". We measured passive mechanics to test the hypothesis that Youngs Modulus and stress would be greater in fibers from trained versus untrained participants and both would be reduced following fatigue. We further assessed the translation of these findings to composite tissue in a sub-set of volunteers where muscle tissue bundles, containing both fibers and extracellular matrix, were analyzed in addition to single fibers. We report a main effect of training such that cellular passive mechanical measures were increased in single fibers from trained versus untrained participants. We likewise report reductions in passive mechanical measures following fatiguing exercise. Surprisingly, both training and acute fatigue only impacted muscle fiber passive measures in males, whereas females showed a more variable response across conditions. Last, we provide preliminary evidence supporting the translation of per-individual cellular differences to the tissue level. Together, these data suggest males respond more dynamically to acute and chronic stressors of muscle tissue mechanics, potentially linking cellular response and sex-dependent differences in musculotendinous injury risk. New and noteworthyWe report that passive stress and modulus in single muscle fibers was higher in resistance trained healthy adults and fatiguing exercise reduced passive stress and modulus. In each case, dynamic responsiveness of muscle fibers to chronic and acute stressors was observed consistently in males, whereas responses in females varied considerably. We provide further evidence that cellular mechanisms may contribute to multicellular muscle tissue samples, suggesting these findings have relevance to in vivo tissue mechanics.

biophysics↗

bioRxiv2024

Fatiguing Exercise Reduces Cellular Passive Young's Modulus in Human Vastus Lateralis Muscle

Previous studies demonstrated that acute, exercise-induced fatigue transiently reduces whole-muscle stiffness. Because reduced muscle stiffness at fatigue may contribute to increased injury risk and impaired contractile performance, the present study seeks to elucidate potential intracellular mechanisms underlying these reductions. To that end, cellular passive Youngs Modulus was measured in single, permeabilized muscle fibers from healthy, recreationally-active males and females. Eight volunteers (4 male, 4 female) completed unilateral, repeated maximal voluntary knee extensions until fatigue, after which percutaneous needle biopsies were performed on the fatigued (F) and non-fatigued (NF) Vastus Lateralis muscles. Muscle samples were processed for mechanical assessment and separately for imaging and phosphoproteomics. Single fibers were passively (pCa 8.0), incrementally stretched to 156% of the initial sarcomere length to assess Youngs Modulus, calculated as the slope of the resulting stress-strain curve at short (strain = 1.00-1.24 %Lo) and long (strain = 1.32-1.56 %Lo) fiber lengths. Titin phosphorylation was assessed by liquid chromatography followed by high-resolution mass spectrometry (LC-MS). Passive modulus was significantly reduced by fatigue at short and long lengths in male, but not female, participants. Fatigue increased phosphorylation of four serine residues located within the elastic region of titin and reduced phosphorylation at one serine residue but did not impact active tension nor sarcomere ultrastructure. Collectively, these results suggest muscle fatigue reduces cellular passive modulus in young males, but not females, concurrent with altered titin phosphorylation. These results provide mechanistic insight contributing to the understanding of sex-based differences in soft tissue injury and falls risk. Key Points SummaryO_LIPrevious studies have shown that skeletal muscle stiffness is reduced following a single bout of fatiguing exercise. C_LIO_LILower muscle stiffness at fatigue may increase risk for soft-tissue injury, however, the underlying mechanisms of this change are unclear. C_LIO_LIOur findings show that fatiguing exercise reduces passive Youngs modulus in skeletal muscle cells from males but not females, suggesting that intracellular proteins contribute to reduced muscle stiffness with fatigue in a sex-dependent manner. C_LIO_LIThe phosphorylation status of the intracellular protein titin is modified by fatiguing exercise in a way that may contribute to altered muscle stiffness after fatiguing exercise. C_LIO_LIThese results provide important mechanistic insight that may help explain why biological sex impacts risk for soft tissue injury in with repeated or high intensity mechanical loading in athletes and falls risk in older adults. C_LI New and NoteworthyMuscle fatigue has previously been shown to reduce musculotendinous stiffness, but the underlying mechanisms remain unclear. Our study presents novel evidence of fatigue-induced reductions in passive cellular Youngs Modulus in skeletal muscle from males, but not females, in conjunction with fatigue-induced alterations in titin phosphorylation. Collectively, these results suggest that intracellular mechanisms including titin phosphorylation may contribute to altered skeletal muscle stiffness following fatiguing exercise, and that this response is mediated by biological sex.

biophysics↗