Muscle Recovery Research Articles

EFEITO DO LACTATO NA REGENERAÇÃO MUSCULAR EM MODELOS IN VIVO E IN VITRO: UMA REVISÃO SISTEMÁTICA

Introduction: Lactate is a substance that, over the years, has been responsible for numerous effects, mainly linked to muscle fatigue, being recently highlighted in systemic processes and muscle regeneration, which still has many points to be clarified, one of them being the participation of lactate in this process. Objective: Verify the effect of lactate on muscle recovery in in vivo and in vitro models. Methods: The search was conducted in five databases (16 June 2022) (PROPERO nº CRD42020209324), using the search words in English and Portuguese: ‘lactate’, ‘lactic acid’, ‘muscle regeneration’, ‘MyoD protein’, and ‘myogenin’. We included experimental and in vitro studies that investigated the use of lactate in relation to muscle (all species and both sexes – males and females). The methodological quality was assessed by a specific questionnaire for in vitro and in vivo studies. Results: Eight articles were selected, of which three studies were found exclusively in vitro, one exclusively in animal models, and four studies with in-vitro models and animal models. Three studies scored overall methodological quality above 90%, another three between 80-90% and two between 70-75%. Both types of studies showed results that may point to the mechanism by which lactate acts in the proliferation and differentiation of myoblasts, either by the action of myogenic regulatory factors (MRFs) or by the actions in the metabolism of these cells. Conclusion: The lactate presence in myoblasts strongly suggests a correlation with the expression of regulatory molecules during muscle regeneration. Future studies must investigate this correlation to advance our understanding of the regulatory mechanisms involved in this process

Macrophage scavenger receptor-A1 promotes skeletal muscle regeneration after hindlimb ischemia.

Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 fl/fl mice, the Lyz Cre/+/SR-A1 flox/flox (SR-A1 ΔMΦ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 ΔMΦ mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 fl/fl mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with in vivo findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 -/- bone marrow macrophage significantly inhibited myoblast differentiation in vitro. Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.

The influence of traditional Thai massage on recovery from gastrocnemius muscle fatigue: A single-blind randomised controlled trial

ObjectiveTo determine the effects of traditional Thai massage (TTM) on improving fatigue recovery and fatigue-related parameters of the gastrocnemius muscle after a heel-raise exercise. DesignA single-blind randomised controlled trial. SettingMae Fah Luang University Hospital, Thailand. ParticipantsFifty-four healthy participants were randomly assigned to two groups: TTM (n = 27; 51.85 % women; mean age 23.15 ± 4.90 years; number of exercises/week: 4.78 ± 1.58) and control (n = 27; 59.26 % women; mean age 22.63 ± 4.88 years; number of exercises/week: 4.48 ± 1.25). InterventionsAfter the participants performed a heel-raise exercise to induce fatigue of the gastrocnemius muscle, they received either 30 min of TTM to the gastrocnemius muscle or 30 min of control (29 min of rest and 1 min total gastrocnemius stretching). Outcome measuresThe outcome measures were the median frequency (MDF) of the electromyography signal, muscle power (MP) and feelings of muscle fatigue (FMF). All the outcome measures were evaluated before (T1) and after (T2) the fatigue-inducement protocol as well as immediately (T3), 1 h (T4) and 2 h (T5) after the interventions. ResultsThe results show that MDF and MP were significantly increased and FMF significantly decreased in both groups immediately after the interventions and at 1 h and 2 h after the interventions (repeated measures ANOVA: p < .05). In the between-group comparisons, participants in the TTM group showed significantly greater improvement than those in the control group on all outcomes at all post-intervention assessment time points (T3, T4, T5), reflecting faster recovery from muscle fatigue (ANCOVA: p < .05). ConclusionTTM proved an effective intervention for maximising recovery from fatigue of the gastrocnemius muscle.

Peroneus Longus Tendon Autografts have Better Graft Diameter, Less Morbidity, and Enhanced Muscle Recuperation than Hamstring Tendon in ACL Reconstruction.

Recently the peroneus longus tendon (PLT) gained popularity in anterior cruciate ligament (ACL) reconstruction and has been utilized with satisfactory outcomes. However, there are concerns regarding donor site morbidity. This study aims to compare the functional outcome of ACL reconstruction using hamstring (HT) and PLT autografts and evaluate the donor site morbidity. Patients who underwent ACL reconstruction were allocated to two groups (HT and PLT). Graft diameter was measured intraoperatively. Knee functional outcome was evaluated with IKDC and Tegner-Lysholm scores preoperatively, and postoperatively after 3 months, 6 months, and 1 year. Donor site morbidities were assessed with thigh circumference measurements, subjective evaluation of sensory disturbances, and ankle scoring with AOFAS and FADI scores. At 1-year follow-up, the PLT group showed comparable IKDC (p = 0.925) and Tegner-Lysholm (p = 0.600) scores with those of the HT group. The mean graft diameter in the PLT group (7.93 ± 0.52mm) was larger compared with the HT group (7.43 ± 0.50mm) (p < 0.001). The incidence of thigh atrophy (HT-16.7%, PLT-10%) and sensory disturbances (HT-73.3%, PLT-10%) was greater in the HT group. There was no significant ankle donor site morbidity in the PLT group (AOFAS-98.67 ± 3.45, FADI-99.23 ± 1.69). ACL reconstruction with PLT had comparable functional outcome with that of HT at 1 year. However, PLT demonstrated larger graft diameter, less donor site morbidity, and enhanced muscle recovery without significantly affecting the ankle function. PLT can be safely used as an acceptable alternative graft choice harvested from outside the knee for ACL reconstruction.

Can pre-exercise photobiomodulation improve muscle endurance and promote recovery from muscle strength and injuries in people with different activity levels? A meta-analysis of randomized controlled trials.

Photobiomodulation therapy (PBMT) was introduced as an ergogenic aid for sport performance in healthy individuals is still controversial. The main aim of this study is to assess the potential enhancements in muscle endurance and recovery from muscle strength and injuries mediated by PBMT among individuals exhibiting diverse activity levels. Randomized controlled trials (RCT) of PBMT interventions for healthy people (both trained and untrained individuals) exercising were searched (up to January 16, 2024) in four electronic databases: Web of Science, PubMed, Scopus and Embase. Primary outcome measures included muscle endurance, muscle strength and creatine kinase (CK) levels; secondary outcome measure included Lactate dehydrogenase (LDH) levels. Subgroup analyses based on physical activity levels were conducted for each outcome measure. Thirty-four RCTs were included based on the article inclusion and exclusion criteria. Statistical results showed that PBMT significantly improved muscle endurance (standardized mean difference [SMD] = 0.31, 95%CI 0.11, 0.51, p < 0.01), indicating a moderate effect size. It also facilitated the recovery of muscle strength (SMD = 0.24, 95%CI 0.10, 0.39, p < 0.01) and CK (mean difference [MD] = -77.56, 95%CI -112.67, -42.44, p < 0.01), indicating moderate and large effect sizes, respectively. Furthermore, pre-application of PBMT significantly improved muscle endurance, recovery of muscle strength and injuries in physically inactive individuals and athletes (p < 0.05), while there was no significant benefit for physically active individuals. Pre-application of PBMT improves muscle endurance and promotes recovery from muscle strength and injury (includes CK and LDH) in athletes and sedentary populations, indicating moderate to large effect sizes, but is ineffective in physically active populations. This may be due to the fact that physically active people engage in more resistance training, which leads to a decrease in the proportion of red muscle fibres, thus affecting photobiomodulation.

Unlocking Strength: The Powerful Impact of Ashwagandha (Withania somnifera) Supplementation on Resistance Training

Withania somnifera, commonly known as ashwagandha, has gained popularity in recent years among individuals interested in healthy lifestyles, natural medicine, and sports. This review aims to summarize the current knowledge regarding the effects of ashwagandha supplementation on various aspects of physical performance, particularly in the context of resistance training. Studies have shown that ashwagandha can positively impact muscle strength, with significant increase of muscle force and power output. Additionally, it has demonstrated potential in modulating body composition, with reduction of body fat percentage noted in certain populations. However, results of studies on ashwagandha’s effect on muscle size remain inconclusive and may depend on various factors such as training status and individual responses. In terms of endurance, ashwagandha supplementation has been associated with improvement in maximal oxygen uptake, indicating enhanced aerobic capacity and delayed exhaustion during endurance activities. Furthermore, ashwagandha was shown to aid muscle recovery by reducing exercise-induced muscle damage and inflammatory response, potentially accelerating the muscle regeneration process. Ashwagandha may also influence hormone levels, such as testosterone and cortisol, with potential implications for muscle growth and recovery. However, further research is needed to fully understand the mechanisms underlying these effects. Overall, ashwagandha supplementation appears to hold promise for enhancing physical performance and overall well-being. Further research is needed to elucidate optimal dosages, long-term safety, and potential interactions with other supplements or medications.

Deciphering the Therapeutic Role of Lactate in Combating Disuse-Induced Muscle Atrophy: An NMR-Based Metabolomic Study in Mice.

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.

Application of near-infrared spectroscopy to assess the effect of the cupping size on the spatial hemodynamic response from the area inside and outside the cup of the biceps.

Cupping therapy is a popular intervention for improving muscle recovery after exercise although clinical evidence is weak. Previous studies demonstrated that cupping therapy may improve microcirculation of the soft tissue to accelerate tissue healing. However, it is unclear whether the cupping size could affect the spatial hemodynamic response of the treated muscle. The objective of this study was to use 8-channel near-infrared spectroscopy to assess this clinical question by assessing the effect of 3 cupping sizes (35, 40, and 45 mm in inner diameter of the circular cup) under -300 mmHg for 5 min on the muscle hemodynamic response from the area inside and outside the cup, including oxyhemoglobin and deoxy-hemoglobin in 18 healthy adults. Two-way factorial design was used to assess the interaction between the cupping size (35, 40, and 45 mm) and the location (inside and outside the cup) and the main effects of the cupping size and the location. The two-way repeated measures ANOVA demonstrated an interaction between the cupping size and the location in deoxy-hemoglobin (P = 0.039) but no interaction in oxyhemoglobin (P = 0.100), and a main effect of the cup size (P = 0.001) and location (P = 0.023) factors in oxyhemoglobin. For the cupping size factor, the 45-mm cup resulted in a significant increase in oxyhemoglobin (5.738±0.760 μM) compared to the 40-mm (2.095±0.312 μM, P<0.001) and 35-mm (3.134±0.515 μM, P<0.01) cup. Our findings demonstrate that the cupping size and location factors affect the muscle hemodynamic response, and the use of multi-channel near-infrared spectroscopy may help understand benefits of cupping therapy on managing musculoskeletal impairment.

Nerve transfer for upper extremity reanimation in people with spinal cord injury: A 2-year follow-up case series

Objective To describe the 2-year functional outcomes of nerve transfer (NT) for upper extremity reanimation. Study Design A prospective case series. Setting A highly specialized rehabilitation hospital for spinal cord injury (SCI) in Italy. Intervention Upper limb nerve transfer (32 NTs, 15 upper limbs). Participants Twelve male individuals with traumatic SCI (AIS A or B, neurological level from C4 to C7) were enrolled; 24-month follow-up data were available for 11. Outcome measures We evaluated the strength recovery of recipient muscles through the Medical Research Council (MRC) Scale for Muscle Strength. Upper limb function and independence were assessed with the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) test version 1 and the Spinal Cord Independent Measure III (SCIM III). Patient satisfaction was also evaluated. Results After 24 months, median MRC scores (range) were: triceps 2 (1–2); extensor digitorum communis 3 (1–4); extensor pollicis longus 2.5 (1–4); flexor digitorum profundus 2 (0–4); flexor pollicis longus 2 (0–4). No complication occurred. GRASSP prehension ability and prehension performance total scores significantly improved at 24 months from 1 (0–4) to 2 (0–7) and from 1 (0–8) to 5 (0–-22), respectively. The SCIM III self-care sub-scale score improved at 24-month follow-up (p = 0.009). This study has important limitations, including a limited generalizability of the results and a small sample size that does not allow definitive conclusions to be drawn. A large multicenter prospective study is needed to confirm our findings. Conclusions NT represents a functional surgery option with few complications for the resuscitation of upper limbs in persons with tetraplegia.

Acute Hypoxia Following Disuse Atrophy in Aged Mice Enhances Cellular Remodeling and Whole-body Strength During Early Recovery

Age-related impairments in muscle recovery following disuse atrophy are associated with altered macrophage metabolism and blunted inflammatory function. HIF-1α is a key regulator of macrophage metabolism and inflammatory function. Therefore, we investigated the effects of acute hypoxia on muscle recovery following disuse in aging. We hypothesized that transient hypoxic exposure following disuse in aged mice would enhance macrophage metabolism and inflammatory status, resulting in improved muscle cellular remodeling and recovery. Accordingly, old (~20 months) and young adult male mice (~4 months) were exposed to acute (24 hours) normobaric hypoxia (8% O2) immediately following 14-days hindlimb unloading. We characterized muscle phenotype and function during early recovery (4- and 7-days) with and without hypoxia exposure. We found that acute hypoxia stimulated the expression of inflammatory (TNF-α, VEGF p&lt;0.01) and glycolytic transcripts (PFK-1 p&lt;0.05), LDH, PDH p=0.08) downstream of HIF-1α in aged skeletal muscle under basal conditions. Following disuse atrophy, transient hypoxic exposure enhanced macrophage inflammatory function, indicated by increased phagocytosis capacity (p&lt;0.01), and promoted early skeletal muscle cellular remodeling events, including enhanced muscle satellite cell content (p&lt;0.05). Furthermore, these effects facilitated the recovery of whole-body strength in aged mice indicated by a return to baseline values (p&gt;0.05). The results of this investigation suggest that hypoxic exposure following disuse atrophy promoted inflammatory macrophage function, muscle cellular remodeling, and enhanced early recovery in aged mice. These findings elucidate the potential benefits of hypoxia in manipulating macrophage function to ameliorate age-related deficits in muscle recovery following disuse atrophy. This research was supported by R01AG076075 (MJD) and the National Institutes of Health Ruth L. Kirschstein National Research Service Award 5T32DK091317 from the National Institute of Diabetes and Digestive and Kidney Diseases. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Persistent Skeletal Muscle Overexpression of Inflammatory Lipid Mediators After Disuse Corresponds to Impaired Skeletal Muscle Recovery in Aged Mice

Aging is associated with impaired recovery of muscle mass and function after a period of disuse, often leading to an increased risk of falls and fractures. The exact mechanisms behind impaired recovery due to aging after disuse are not fully understood. Membrane-derived lipids mediators (LM) in muscle orchestrate inflammatory actions that are critical for restoration of muscle following injury. We tested the hypothesis that muscle LM associated with inflammation would be dysregulated in adult vs older mice during a time course of recovery following disuse atrophy. Therefore, we designed a study in which adult (3-6m/o) and old (23-26m/o) male mice underwent 14 days of hindlimb unloading followed by 2, 4, or 7 days of reloading. The gastrocnemius muscle was collected at each timepoint and between age groups and processed for lipidomic analysis of the eicosanoids. Gastrocnemius muscle mass showed impaired recovery after HU in the old group when compared to adult, at 4 (P=0.0420) and 7 days reload (P=0.0092). We also observed that muscle LM’s associated with acute inflammation (arachidonic acid, prostaglandins, leukotrienes) were significantly overexpressed in old mice during recovery after disuse. Importantly, several of these lipids corresponded with impaired muscle recovery. PGE2 and PGF2a levels showed a correlation (P=0.03 and P=0.02, respectively) with gastrocnemius mass at the 4 days reload. We conclude that recovery from disuse in aged mice are characterized with the upregulation of pro-inflammatory lipids in muscle and this may be related to poor muscle regrowth. Future studies will be considered to determine the role and cell source of these pro-inflammatory LM during muscle recovery in aged mice. Funding was provided by NIH: R01AG076075 awarded to M.J.D. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 2030: Endothelial Deletion Of Bag3 Does Not Impair Ischemic Limb Recovery In A Murine Model Of Peripheral Artery Disease

Background: Peripheral artery disease (PAD) is a highly prevalent vascular occlusive disease which mostly affects the lower limb. Emerging studies proved the critical functions of endothelial cells in arteriogenesis and ischemic limb blood flow recovery. However, very few targets with endothelial cell exclusivity have been identified. Here, we explored the role of endothelial BCL-2 associated athanogene 3 (Bag3) in ischemic limb recovery. Hypothesis: We hypothesized that the loss of endothelial specific BAG3 would attenuate blood flow and muscle recovery following HLI. Methods: Hind limb ischemia (HLI) was induced in Bag3 Cdh5(PAC)-CreERT2 male and female mice after tamoxifen (2mg/day x 5 days) or vehicle treatment ( n ≥12/group). Limb blood flow was measured by laser Doppler perfusion imaging (LDPI) and isometric muscle force production, vascular density and muscle morphology were assessed after HLI. Results: LDPI analysis revealed no differences in the blood flow between groups at HLI d7 ( n=9 ; day 7, 21.86% ischemic/non-ischemic ± 3.80% vs 18.05% ± 1.96% SEM; p=0.05). There was no deficit in isometric force recovery of the EDL ( n ≥12; 57.76 ± 15.92 vs 83.05 ± 27.12 SEM; p =0.05) in KO animals at HLI d7. Similar rates of CD31+ vessel disorganization was observed in both groups at HLI d7, ( n =7; 4626.0 um 2 CD31+ area ± 869 vs 4870.9 ± 1056 SEM) consistent with recovering ischemic tissue. There were also no differences in blood flow recovery assessed by LDPI at HLI d28 ( n =7; 50.74% ischemic/non-ischemic ± 7.4% vs 59.17 ± 8.21; n=9). Conclusions: Endothelial cell specific Bag3 knockout did not impair vascular morphology or perfusion recovery at baseline or following HLI in a murine model of peripheral artery disease. No differences in muscle morphology or contractile function at baseline or after HLI at either timepoint were observed. In summary, we reveal an unexpectedly minor role of endothelial cell BAG3 in tissue recovery following ischemic injury.

Abstract 3026: Genetic Deletion Of Skeletal Muscle Bag3 Exacerbates Ischemic Myopathy

Background: Bcl2-associated athanogene 3 (BAG3) is a multifunctional adaptor protein that regulates diverse cellular functions. Mutations in BAG3 are causally linked to myofibrillar myopathy and dilated cardiomyopathy in humans and now appear to be one of the most common to cause human disease. We previously identified a murine coding variant in Bag3 that contributes to hindlimb ischemia (HLI) pathology, however, no cell specific data on Bag3’s role in PAD pathology exists. Hypothesis: We hypothesized that muscle specific BAG3 is required for both the restoration of blood flow and muscle recovery following HLI. Methods: We generated a genetic model of lifelong muscle cell (mature fiber and progenitor) Bag3 deletion (Pax7-Cre; Bag3 -/- ) on a BL6 parental background. Male and Female mice (12-20 weeks; WT: n=45; KO: n=32) were evaluated at baseline and HLI d7 and d28 for blood flow via LDPI, isometric muscle force production, vascular density and muscle morphology. Bag3 deletion was validated by recombination, qRT-PCR and Western Blotting in whole tissue, isolated myofibers, and FACS muscle progenitor cells. Results: KO reduced muscle force production (n=18; 145.8mN Force ± 28.6 vs 56.9 ± 16.8 SEM; p=0.0208) and capillary perfusion (n=7; 0.17 CD31+/Lectin+ vessels ± 0.02 vs 0.09 ± 0.01 SEM p=0.0491) indicative of the multi-compartmental effect of BAG3 loss in skeletal muscle at HLI d7. Extended HLI (d28) revealed a KO phenotype characterized by reduced blood flow recovery (LDPI; n= 7; .68 ischemic/non limb ± 0.5 vs .38 ± 0.6 SEM p=0.0011) and sustained myopathy including reduced myofiber size ( n =7; 1585um 2 ± 161 vs 1093 ± 169 SEM; p =0.05) and increased tissue lesion size ( n =7; 2.5% muscle area ± 2.0 vs 48.3% ± 21.6; p =0.03). Conclusion: Loss of skeletal muscle Bag3 exacerbates myopathy and reduces capillary perfusion and blood flow recovery following HLI and demonstrate a requirement for BAG3 in recovery from limb ischemia.

Investigating the Effect of Rapamycin on Impaired Proteostasis in Aged Skeletal Muscle After Disuse Atrophy

Older individuals undergo loss of muscle mass and strength, which can be compounded during bed rest and extended hospital stays. Adult and aged individuals lose muscle mass at similar rates during periods of disuse; however, only aged skeletal muscle fails to fully recover once activity resumes. Current efforts to facilitate skeletal muscle recovery are aimed at increasing myofibrillar protein synthesis by stimulating mTORC1(mammalian target of rapamycin complex 1), a major regulator of protein synthesis. However, we showed that skeletal muscle in aged rats already has higher rates of myofibrillar protein synthesis and mTORC1 activity than adult rats. We also showed that aged skeletal muscle has an accumulation of insoluble ubiquitinated proteins compared to adult muscle, indicating impaired proteostasis and possibly impaired autophagy degradation. We hypothesized that mTORC1 inhibition via rapamycin administration would reduce protein synthesis and the accumulation of p62 aggregates, facilitating recovery in aged skeletal muscle after disuse. Methods: Adult (10 months) and old (26 months) OKC HET rats were hindlimb unloaded (HU) for 14-days to induce atrophy, followed by subsequent 14 days of reloading (RE) through normal ambulation. Animals were fed either a control or rapamycin-supplemented (42 ppm) diet. To determine bulk protein synthesis, rats were labeled with deuterium oxide (D2O) during weight bearing (WB), HU, and RE, (n=4-6 per time point per group). Finally, to assess the presence of autophagy related protein aggregates we immuno stained for Sequestosome 1/p62, an autophagy cargo receptor protein. Results: Our data showed that myofibrillar protein synthesis rates were elevated in the old muscle compared to the adult ( k = 0.029 1/day ±0.002 vs. 0.039 1/day ±0.002, p&lt;0.0001), and that protein synthesis rates were lower in the old rapamycin cohort (k = 1/day ±0.002 vs. 1/day ±0.003, p&lt;0.0001). Furthermore, p62 puncta was three-fold more abundant (p&lt;0.01) in aged skeletal muscle, compared to the adult muscle. Although the sample size is small, when comparing p62 puncta in the old rapamycin group to the old controls, there was no difference between the cohorts. Conclusion: We show that mTORC1 inhibition reduces protein synthesis in aged skeletal muscle. We also show that aged muscle has more p62 aggregates compared to adult skeletal muscle, indicating that autophagy related targets are not being degraded effciently with age. Further analyses will assess the effects of mTORC1 inhibition on other proteostatic mechanisms in atrophied skeletal muscle of aged rats. NIA Training Grant: 5T32AG052363-04VA I01 BX005592 APS SURF. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Rehabilitation Guidelines on Mothers' Knowledge, Practice and Functional Recovery of Facial Muscles for Their Children with Bell's Palsy

Effect of Rehabilitation Guidelines on Mothers' Knowledge, Practice and Functional Recovery of Facial Muscles for Their Children with Bell's Palsy

Skeletal muscle proteomics responses in men and women during acute exercise-heat stress and acclimation

Purpose: Our broad aim was to identify targetable mechanisms of improving skeletal muscle function and recovery during exercise-heat stress. In this study, we used proteomics to test the hypothesis that skeletal muscle proteomic changes would correspond to acclimation state. Methods: Healthy men (M: n = 7, 22 ± 2 yo, VO2max 52.86 ± 2.35 ml·kg−1·min−1) and women (F: n = 7, 24 ± 1 yo, VO2max 45.97 ± 2.57 ml·kg−1·min−1) completed a 5-day heat acclimation (HA) (40 °C, 40% rH). Before and after HA, participants completed a heat tolerance test measuring time to reach rectal temperature 39.5°C (HTT39.5) or failure (stoppage). Musculoskeletal biopsies from the vastus lateralis were harvested for protein extraction, quantification, and digestion prior to untargeted UPLC-MS/MS (Q Exactive HF). Peptide identification and label-free quantitation was achieved using Andromeda search engine and MaxQuant (v1.6.10.43), using UniProt reference proteome UP0000005640. All search results were filtered to FDR (false discovery rate) 1% and uploaded to Scaffold v5.1.0 for data visualization and t-test analyses for difference between conditions (p &lt; 0.05). Functional annotation and pathway analysis were conducted (DAVID, Reactome, String). Physiological, perceptual, and performance metrics were statistically analyzed using t-tests (p ≤ 0.05). Results: No significant differences (p = 0.931) were observed between males (mean = 27.21 ± 1.37 minutes) and females (26.91 ± 3.20 minutes) for PREHA HTT39.5. HTT39.5 for F was significantly higher than for men at PREHA (p = 0.001) and POSTHA (p = 0.014). 2741 proteins from 960,731 spectra were detected among our skeletal muscle biopsy samples with 22 and 33 proteins expressed more highly in M and F at PREHA, respectively. 149 and 81 proteins were more highly expressed in M and F, respectively, at POSTHA. Differences between M and F included more highly connected nodes in M at PREHA (average node degree: 3.7, avg. local clustering coeffcient: 0.529, PPI enrichment p-value &lt; 1.11e-16, HIST1H3 (isoforms D, H, and J), HIST1H4F, HIST2H2A (isoforms C, B, and E), HIST2HAC, H2AFX) and at POSTHA (average node degree: 4.26, avg. local clustering coeffcient: 0.455, expected number of edges 110, PPI enrichment p-value &lt; 1.0e-16, GAPDH, RPS13, TPI1, PKM, RPS21). Differences in F and M (more highly expressed) also included GO terms related to DNA, RNA, and protein quality regulation and immune function and metabolism (p &lt; 0.05). Conclusions: Acclimation is associated with different skeletal muscle responses in M and F related to protein synthesis and immune function pathways that are regulated after a bout of exercise-heat stress. Ongoing analysis examines relationships between naïve or acclimated state and individual skeletal muscle proteomic profiles. DoD BA200299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of a graded running race on lower limb muscle damage, jump performance and muscle soreness in men and women.

Delayed structural and functional recovery after a 20 km graded running race was analyzed with respect to the sex effect. Thirteen female and 14 male recreational runners completed the race and three test sessions: one before (PRE) and two after, once on Day 1 or 2 (D1-2) and then on Day 3 or 4 (D3-4). Muscle damage was assessed indirectly using ultrasonography to quantify changes in cross-sectional area (CSA) of 10 lower-limb muscles. Delayed onset of muscle soreness (DOMS) was assessed for three muscle groups. Functional recovery was quantified by kinetic analysis of a squat jump (SJ) and a drop jump (DJ) test performed on a sledge ergometer. Linear mixed models were used to assess control group reproducibility and recovery patterns according to sex. Regardless of sex, DOMS peaked at D1-2 for all muscle groups and resolved at D3-4. CSA was increased in each muscle group until D3-4, especially in the semimembranosus muscle. A specific increase was found in the short head of the biceps femoris in women. Regardless of sex, SJ and DJ performances declined up to D3-4. Depending on the muscle, positive and/or negative correlations were found between structural and functional changes. Some of these were sex-specific. Structural and functional recovery was incomplete in both sexes up to D3-4, although DOMS had disappeared. More emphasis should be placed on hamstring muscle recovery. Highlighting the intermuscular compensations that can occur during multi-joint testing tasks, the structural-functional relationships were either positive or negative, muscle- and sex-dependent.

Development of an Exercise-based EV Therapy to Improve Skeletal Muscle Recovery After Immobilization

Introduction: Immobilization is necessary for recovery from illness or bone fractures; however, prolonged immobilization can result in significant loss of muscle mass and function. It is critical to recover muscle mass quickly following immobilization as severe muscle atrophy is correlated with increased likelihood of metabolic disorders, disability, and mortality. Physical rehabilitation can improve outcomes but is not always feasible. The purpose is to determine the extent to which EVs circulating in blood after endurance exercise training (EnVs) act as a safe and effective therapy to recover skeletal muscle mass following disuse. Methods: Donor C57BL/6 mice (n = 8-10, 4-month-old) were provided access to horizontal running wheels in a locked (sedentary) or unlocked (exercise) condition. After 4 weeks of voluntary running, EVs (SedVs or EnVs) were isolated from plasma using size exclusion chromatography according to manufactures guidelines, and concentration confirmed via nanoparticle tracking analysis (NanoSight NS3000). Recipient C57BL6/J mice (n = 5-8, 4-month-old) were subjected to single limb immobilization for 14 days. Upon remobilization, mice received a single intramuscular injection of PBS, SedVs, EnVs, or endurance plasma proteins, and remobilized for 3 and 14 days. Muscle samples were collected after remobilization and assessed for muscle cross-sectional-area (CSA) and capillarization. Results: Upon 3-day remobilization, EnVs did not significantly recover global fiber CSA and fiber-type specific CSA (Type IIa, Type IIx or Type IIb) or capillarization. Upon 14-day remobilization, EnVs did not significantly improve global fiber CSA and fiber-type specific CSA. However, a significant treatment effect was observed for capillary density (P = 0.0445), with increases observed for both SedV (P = 0.034) and EnV (P = 0.0117). Conclusion: EVs isolated from plasma after exercise can significantly improve skeletal muscle vascularization after immobilization, which may represent an important step toward full recovery of skeletal muscle mass. Partially support by NIH (NIAMS R01AR072735). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Characterizing the association of systemic estradiol levels and transcriptional markers of skeletal muscle regeneration in healthy young females

Recent research indicates estradiol's (E2) role in modulating skeletal muscle regeneration. E2 has been observed to enhance myogenic capacity by upregulating myogenic factors and downregulating proteolytic factors[1,2]. The extracellular matrix (ECM) of skeletal muscle also influences regeneration due to its interaction with muscle progenitor cells [5]. Cell and animal studies observed E2's ability to impact on collagen (COL) 1, 3, and 4 production [3,4]. However, limited data from physiologically relevant human models exploring myogenic markers and ECM throughout the menstrual cycle are available. We hypothesize that higher systemic E2 levels will correspond to an increased regenerative gene expression signature. Understanding this relationship is crucial for assessing how E2 levels affect muscle healing in eumenorrheic women and E2’s potential as a therapeutic molecule for enhancing muscle repair. The study included 19 pre-menopausal women aged 18-39 undergoing hip surgery at UT Southwestern (UTSW) Medical Center. This study was approved by the UTSW IRB and conducted in accordance with the Declaration of Helsinki. Blood and muscle biopsies were collected for hormone and gene analysis. Only subjects in the follicular phase (n=12) were included to minimize progesterone's influence. Investigated genes included myogenic factors (MYOD1, MYF5, MYF6, MYOG), proteolytic factors (FOXO3, MuRF1), and COL genes (COL1a1, COL-3a1, COL-4a1, COL-6a1). E2 levels ranged from 26-356 pg/mL, with negligible progesterone levels, consistent with the follicular phase. While no significant relationships were found between myogenic and proteolytic genes, MYF6 exhibited a positive relationship with E2 (p=0.07), while MuRF1 showed a negative one (p=0.09). COL 1, 3, and 6 gene expressions had no significant relationship with E2, but COL 4 exhibited a statistically significant positive relationship (p=0.04) with E2 concentration. Though no statistically significant relationships emerged between myogenic or proteolytic gene expression and E2 levels, there were notable trends toward significance for MYF6 and MuRF1. MYF6, recognized for its role in myogenic differentiation, is implicated in maintaining the satellite cell pool by promoting myokine secretion[6]. In contrast, MuRF1 is a critical component in muscle atrophy[7]. COL4 expression was significantly associated with E2 levels (p=0.4). It is hypothesized that COL4 enhances IGF1-activated myoblast migration, differentiation, and fusion [5]. These findings suggest a potential link between elevated E2 levels and an enhanced regenerative capacity. These findings indicate that higher E2 conditions may create a favorable environment for muscle recovery. Future research should increase sample size and examine protein levels of these factors.

Resistance-Exercise-Induced Circulating Factors on Damaged Skeletal Muscle Tissue Proteome in Young Untrained Men

Recovery from muscle damage is tightly orchestrated by multiple physiological processes that can be altered by circulating factors (e.g., cytokines, growth factors) and intracellular signaling pathways (e.g., autophagy). Our previous studies have demonstrated that resistance exercise (RE)-induced circulating factors alter the expression of intramuscular cytokine mRNA and autophagic and myogenic markers in exercise-induced skeletal muscle damage (EIMD). However, the global effects of these circulating factors on damaged muscle are largely understudied. Purpose: To identify global changes in the proteome and functional pathways in skeletal muscle when EIMD is followed by an upper body RE-induced circulating milieu. Hypothesis: RE-induced circulating factors alter protein expression profile in damaged muscle. Methods: Vastus lateralis samples from 3 men included in the parent study were utilized for this report. Untrained men (age: 23 ± 5yr; height: 181.6 ± 5.9cm; weight: 86.0 ± 15.8kg) completed 2 identical bouts of maximal unilateral eccentric knee extensions for 8 sets of 10 repetitions, which were immediately followed by either heavy upper body RE to induce changes in circulating factors (EX) or 20 min seated rest (CON). Muscle samples from the damaged leg at 24h were used to compare between conditions. The total number of proteins was measured using LC-MS/MS. Bioinformatic analyses were performed via Qiagen Ingenuity Pathway Analysis software. For identifying enriched biological processes and functions, proteins had to have at least 1.0-fold differential expression with an FDR-adjusted significance level &lt; 0.05. Z scores were calculated to predict changes in biological functions. Results: A total of 900 proteins were identified. For EX, 79 proteins were downregulated, and 15 were upregulated compared to CON at 24h. Pathway analyses demonstrated that for EX, there was decreased activation in acute phase response signaling, liver X receptor/retinoid X receptor activation, nitric oxide production and reactive oxygen species in macrophages, and neutrophil extracellular trap signaling pathways compared to CON. In addition, for EX, there was an increase in macrophage IL-12 signaling and production than CON. Conclusion: RE-induced changes in circulating factors modulated pathways associated with the immune response and cytokine signaling in untrained men. Given that immune response is critical for recovery from muscle damage, these results highlight the potential role of RE-induced circulating factors (e.g., hormones, growth factors, etc.) which could play a role in mediating muscle recovery. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.