Enhance Muscle Recovery Research Articles

Impact of Resistance Exercise and Nitrate Supplementation on Muscle Function and Clinical Outcomes After Knee Osteoarthritis Surgery in Middle-Aged Women with Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background/Objectives: Sarcopenia, characterized by reduced muscle mass and strength, is associated with osteoarthritis (OA), particularly in middle-aged women, and may worsen postoperatively. Resistance exercise (RE) can resolve sarcopenia; however, recovery is often suboptimal. Nitrate (NO3-) supplementation may enhance muscle recovery and complement RE. We investigated whether NO3- supplementation combined with RE improves thigh muscle mass and strength in middle-aged women during postoperative rehabilitation. Methods: We conducted a prospective randomized placebo-controlled double-blind study including 36 middle-aged women with sarcopenia and cartilage defects undergoing mesenchymal stem cell implantation. Participants were assigned to RE with NO3- supplementation (NG, n = 18) or with placebo (PG, n = 18) groups. Both groups underwent 12 weeks of supervised RE. The primary outcomes were thigh muscle cross-sectional area (CSA) and knee strength, whereas functional and clinical measures, including the Short Physical Performance Battery (SPPB), skeletal muscle index (SMI), International Knee Documentation Committee (IKDC), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, were secondary outcomes. Results: Thigh muscle CSA decreased in the PG but was maintained in the NG. Knee extension strength improved significantly in the NG compared with that in the PG at 6 and 12 weeks. Knee flexion strength also improved rapidly in the NG, with a significant increase at 6 weeks. SPPB and IKDC scores improved significantly in the NG. However, similar improvements were observed for WOMAC scores in both groups. Conclusions: NO3- supplementation combined with RE effectively prevented muscle atrophy and enhanced muscle strength in our study participants, indicating potential for improving postoperative recovery.

Sex-Based Effects of Branched-Chain Amino Acids on Strength Training Performance and Body Composition.

Branched-chain amino acids (BCAAs) are widely studied for their effects on muscle recovery and performance. This study examined the effects of BCAA supplementation on anthropometric data, physical performance, delayed onset muscle soreness (DOMS), and fatigue in recreational weightlifters. The trial involved 100 participants (50 men and 50 women), randomized into BCAA and placebo groups. Subjects in the BCAA group took five daily capsules of 500 mg L-leucine, 250 mg L-isoleucine, and 250 mg L-valine for six months. A two-way ANOVA was used to analyze the main and interaction effects of sex and treatment. Notable findings include significant improvements in muscle recovery, as indicated by reduced DOMS, particularly in women who showed a decrement of 18.1 ± 9.4 mm compared to 0.8 ± 1.2 mm in the placebo group of a horizontal 100 mm line. Fatigue perception was also significantly lower in the BCAA group, with women reporting a greater decrease (2.6 ± 1.5 scores) compared to the placebo group (0.6 ± 0.7 scores). Strength gains were prominent, especially in men, with a 10% increase in bench press maximum observed in the BCAA group. The interaction between sex and treatment was significant, suggesting sex-specific responses to BCAA supplementation. These results underscore the effectiveness of BCAA supplementation in enhancing muscle recovery, reducing fatigue, and improving strength. This study also highlights sex-specific responses, with women benefiting more in terms of DOMS and fatigue reduction, while men experienced greater strength gains, suggesting a need for tailored supplementation strategies.

Biosponge-Encased Placental Stem Cells for Volumetric Muscle Loss Repair.

Objective: Volumetric muscle loss (VML) leads to permanent muscle mass and functional impairments. While mesenchymal stromal cells (MSCs) and their secreted factors can aid muscle regeneration, MSCs exhibit limited persistence in injured tissue post-transplantation. Human placental-derived stem cells (hPDSCs), sharing surface markers with MSCs, demonstrate superior regenerative potential due to their fetal origin. Previously, a biosponge (BS) scaffold was shown to augment muscle regeneration post-VML. This study aims to coapply BS therapy and hPDSCs to further enhance muscle recovery following VML. Approach: A VML defect was created by removing ∼20% of the tibialis anterior muscle mass in male Lewis rats. Injured muscles were either left untreated or treated with BS or BS-encapsulated hPDSCs cultured under normoxic or hypoxic conditions. On day 28 postinjury, peak isometric torque was measured, and the muscle was harvested for analysis. Results: BS encapsulated hPDSCs subjected to hypoxic preconditioning persisted in larger quantities and enhanced muscle mass at day 28 postinjury. BS encapsulated hPDSCs cultured under normoxic or hypoxic conditions increased small myofibers (<500 µm2) percentage, MyoD protein expression, and both pro- and anti-inflammatory macrophage marker expression. BS encapsulated hPDSCs also reduced fibrosis and BS remodeling rate. Innovation: This study is the first to examine the therapeutic effects of hPDSCs in a rat VML model. A BS carrier and hypoxic preconditioning were investigated to mitigate low cell survival postimplantation. Conclusion: hPDSCs augment the regenerative effect of BS. Combining hPDSCs and BS emerges as a promising strategy worthy of further investigation.

Effect of a honey-sweetened beverage on muscle soreness and recovery of performance after exercise-induced muscle damage in strength-trained females.

This study explores a novel approach to mitigating delayed-onset muscle soreness (DOMS), a common issue among strength-trained females. By investigating the potential of a honey-sweetened beverage, which contains anti-inflammatory properties, we aim to enhance muscle recovery after exercise-induced muscle damage (EIMD). A randomized, cross-over, placebo-controlled, and double-blinded study was conducted with sixteen female strength athletes. Firstly, the baseline measurements were recorded, and participants were randomly divided into two conditions: honey-sweetened beverage (HSB; 70g of honey in 250mL water with a concentration of 28%) and placebo (PLA; 250mL of water with 70g of artificial sweetener). The HSB and PLA were consumed 90min before the EIMD started (200 vertical jumps with 10% body-weighted vests). Recovery monitoring of performance indicators and DOMS was performed after EIMD. The results of wall-sit, V-Sit and reach flexibility test (VSFT), vertical jump height (VJH), pressure pain threshold (PPT), and one repetition maximum (IRM) tests were recorded 48h after EIMD. Also, DOMS was recorded using the visual analog scale (VAS) before the start of the test and immediately, 12, 24, and 48h after EIMD. A one-week interval was considered a washout period for each condition. The collected data were analyzed by repeated measures of ANOVA and Bonferroni post hoc test and dependent t-test at P ≤ 0.05 level. Compared to PLA, HSB ingestion improves wall-sit performance (p = 0.003), 1RM (p = 0.019), and RPE (p = 0.003) after EIMD. However, no significant differences were observed between BL, PLA, and HSB in VJH (p = 0.384), VSFT (p = 0.840), and PPT (p = 0.151) after EIMD. Furthermore, HSB, compared to PLA, considerably decreased the values of DOMS immediately, 12, 24, and 48h after EIMD (p < 0.05). Our findings illustrated that ingesting HSB in strength-trained females can be a helpful strategy for improving recovery indicators such as muscle strength, endurance, and muscle soreness after EIMD.

Effect of L-Citrulline on Creatine Kinase MM (CK-MM) Isoenzymes in Mice: An In Vivo Study Focusing on Immunohistochemistry Analysis

Highlights:1. This study elucidates the effect of L-citrulline supplementation on creatine kinase MM (CK-MM) expression post-eccentric exercise, offering novel insights into its potential role in mitigating muscle damage.2. The findings demonstrate that L-citrulline administration significantly reduces CK-MM expression levels in skeletal muscle tissue, suggesting its therapeutic potential in enhancing muscle recovery and performance following exercise-induced damage.3. This study contributes valuable insights into the multifaceted benefits of L-citrulline supplementation for supporting overall muscle health and performance by identifying its protective effects under different mechanisms, including improved blood flow, antioxidant activity, enhanced mitochondrial function, and promotion of muscle protein synthesis. Abstract Eccentric exercise often induces muscle injuries in athletes, resulting in impaired performance and prolonged recovery time. Creatine kinase MM (CK-MM) is a biomarker for assessing muscle damage, with elevated levels indicating injury. L-citrulline, an amino acid, has shown promise in enhancing performance and reducing recovery time. However, its specific effect on CK-MM remains unclear. This study utilized immunohistochemistry analysis to investigate the effect of L-citrulline supplementation on CK-MM expression post-eccentric exercise in male BALB/c mice. This in vivo study was conducted with a post-test-only design. A total of 25 mice were divided into two control groups (normal/C1 and negative/C2) and three treatment groups (T1, T2, and T3), each containing five mice. The T1, T2, and T3 groups were daily administered 250, 500, and 1,000 mg/kg bw of L-citrulline for seven days, respectively. All mice, except the C1 group, performed a downhill running procedure. The CK-MM expression in skeletal muscle tissue post-eccentric exercise was assessed using immunohistochemistry analysis. The statistical analysis included the Shapiro-Wilk test for data distribution and the Kruskal-Wallis and Mann-Whitney post-hoc tests for significant differences (p&lt;0.05). The results showed that CK-MM expression in the C2 group (91.00±2.24%) was significantly higher (p=0.008) than that of the C1 group (70.00±10.0%). Subsequently, the T1 (68.00±9.08%, p=0.008), T2 (72.00±7.58%, p=0.008), and T3 (67.00±9.75%, p=0.008) groups exhibited significantly lower expressions than the C2 group. These results were consistent with the role of CK-MM as a marker for muscle damage, and they indicated that L-citrulline might have a protective effect against muscle damage post-eccentric exercise. However, no significant differences were observed among the C1, T1, T2, and T3 groups. In conclusion, L-citrulline supplementation demonstrates promise in attenuating muscle damage following eccentric exercise, as evidenced by reduced CK-MM expression levels. These findings highlight the potential therapeutic role of L-citrulline in enhancing muscle recovery and performance.

Unlocking Male Youth Soccer Players’ Peak Performance Potential: Exploring the Impact of Maturation, Age, and Physical Demands on Neuromuscular Injury Risk and Recovery Following Competitive Matchplay

This study investigated the 7-day recovery period post-soccer matches in elite male academy players. We analyzed changes in physical performance, stretch-shortening cycle capability, landing mechanics, muscle damage, and perceived well-being while also considering the influence of players’ maturity status, chronological age, and physical demands on post-match responses. In a prospective, observational, mixed longitudinal study design, twenty-six players (U14 = 14 [age = 13.9 ± 0.2 y, and U16 = 12 [age = 15.1 ± 0.2 y]) undertook testing at baseline (1 h pre-match), immediately post-match (0 h), and 48-, 72-, 96-, and 120 h post-match for measures in creatine kinase (CK), urea (UR), CMJ height, 20 m sprint time, reactive strength index (RSI), leg stiffness (LS), landing mechanics, and perceived well-being. Players were also tested pre [168-h] and post the subsequent match. Results showed significant alterations 0 h post-match in CK (+71.3%), UR (+12.8%), CMJ height (−5.3%), 20 m sprint time (+3.8%), RSI (−9.6%), LS (−11.5%), and perceived well-being (−7.7%), with landing mechanics being unaffected. All parameters returned to baseline at 48 h, except for CK and UR, which remained elevated until 168 h. The players’ initial scores influenced how they responded after the match during the week. In conclusion, coaches should focus on post-match strategies to enhance muscle recovery, especially for youth players with a lower training status, given the extended recovery period observed for muscle damage markers.

Agent-based model demonstrates the impact of nonlinear, complex interactions between cytokinces on muscle regeneration.

Muscle regeneration is a complex process due to dynamic and multiscale biochemical and cellular interactions, making it difficult to identify microenvironmental conditions that are beneficial to muscle recovery from injury using experimental approaches alone. To understand the degree to which individual cellular behaviors impact endogenous mechanisms of muscle recovery, we developed an agent-based model (ABM) using the Cellular-Potts framework to simulate the dynamic microenvironment of a cross-section of murine skeletal muscle tissue. We referenced more than 100 published studies to define over 100 parameters and rules that dictate the behavior of muscle fibers, satellite stem cells (SSCs), fibroblasts, neutrophils, macrophages, microvessels, and lymphatic vessels, as well as their interactions with each other and the microenvironment. We utilized parameter density estimation to calibrate the model to temporal biological datasets describing cross-sectional area (CSA) recovery, SSC, and fibroblast cell counts at multiple timepoints following injury. The calibrated model was validated by comparison of other model outputs (macrophage, neutrophil, and capillaries counts) to experimental observations. Predictions for eight model perturbations that varied cell or cytokine input conditions were compared to published experimental studies to validate model predictive capabilities. We used Latin hypercube sampling and partial rank correlation coefficient to identify in silico perturbations of cytokine diffusion coefficients and decay rates to enhance CSA recovery. This analysis suggests that combined alterations of specific cytokine decay and diffusion parameters result in greater fibroblast and SSC proliferation compared to individual perturbations with a 13% increase in CSA recovery compared to unaltered regeneration at 28 days. These results enable guided development of therapeutic strategies that similarly alter muscle physiology (i.e. converting extracellular matrix [ECM]-bound cytokines into freely diffusible forms as studied in cancer therapeutics or delivery of exogenous cytokines) during regeneration to enhance muscle recovery after injury.

Agent-based model demonstrates the impact of nonlinear, complex interactions between cytokines on muscle regeneration

Muscle regeneration is a complex process due to dynamic and multiscale biochemical and cellular interactions, making it difficult to identify microenvironmental conditions that are beneficial to muscle recovery from injury using experimental approaches alone. To understand the degree to which individual cellular behaviors impact endogenous mechanisms of muscle recovery, we developed an agent-based model (ABM) using the Cellular-Potts framework to simulate the dynamic microenvironment of a cross-section of murine skeletal muscle tissue. We referenced more than 100 published studies to define over 100 parameters and rules that dictate the behavior of muscle fibers, satellite stem cells (SSCs), fibroblasts, neutrophils, macrophages, microvessels, and lymphatic vessels, as well as their interactions with each other and the microenvironment. We utilized parameter density estimation to calibrate the model to temporal biological datasets describing cross-sectional area (CSA) recovery, SSC, and fibroblast cell counts at multiple timepoints following injury. The calibrated model was validated by comparison of other model outputs (macrophage, neutrophil, and capillaries counts) to experimental observations. Predictions for eight model perturbations that varied cell or cytokine input conditions were compared to published experimental studies to validate model predictive capabilities. We used Latin hypercube sampling and partial rank correlation coefficient to identify in silico perturbations of cytokine diffusion coefficients and decay rates to enhance CSA recovery. This analysis suggests that combined alterations of specific cytokine decay and diffusion parameters result in greater fibroblast and SSC proliferation compared to individual perturbations with a 13% increase in CSA recovery compared to unaltered regeneration at 28 days. These results enable guided development of therapeutic strategies that similarly alter muscle physiology (i.e. converting extracellular matrix [ECM]-bound cytokines into freely diffusible forms as studied in cancer therapeutics or delivery of exogenous cytokines) during regeneration to enhance muscle recovery after injury.

The phytochemical composition and unexplored potential of Australian native plants for application in physical activity-related muscle recovery and inflammation: a literature review.

Native plants are adaptable in various environmental conditions in part through the production of unique phytochemicals which may have beneficial effects on human health. Native Australian fruits contain higher phytochemical and antioxidant levels than most Western fruits, suggesting potential for greater health benefits arising from their consumption. These beneficial effects, in turn, may be mediated by the inhibition of inflammatory pathways as well as oxidative stress via the regulation of reactive oxygen (ROS) and/or nitrogen (RNS) species levels. Unaccustomed or strenuous exercise causes muscle damage and soreness, that may be driven by increased ROS and inflammation. There is growing interest in the application of polyphenol-rich food supplementation for the alleviation of exercise-induced oxidative stress, for the reduction of exercise-induced inflammation and improvement of muscle recovery. Therefore, the aim of this review was to provide an overview of the phytochemical and bioactive composition of some Australian native plant foods and their potential use for functional food development in the management of muscle recovery and inflammation. Native plant foods and food products could be beneficial for reducing inflammation, though it is important to note that most of the research in this field has been conducted in animal models or in vitro, in addition to there being little data on skeletal muscle inflammation. Further studies, particularly in humans, would be needed to confirm these effects and to determine the appropriate dosages and forms of native foods and food products for consumption to reduce inflammation and enhance muscle recovery.

Delayed Onset Muscle Soreness (DOMS): Management Update

Delayed Onset Muscle Soreness (DOMS) is a prevalent issue in sports medicine and among physically active individuals, causing significant pain and disability. While the exact pathophysiology of DOMS remains incompletely understood, this article delves into non-pharmacological approaches to effectively manage and alleviate its symptoms.&#x0D; The research discusses multifaceted aspects of DOMS, encompassing its complex etiology, theories, and contributing factors. Numerous theories have been proposed, including delayed inflammatory responses, lactic acid accumulation, muscle spasms, connective tissue damage, and muscle micro-tears. These theories underscore the intricate nature of DOMS and the need for a diverse management approach.&#x0D; The article explores non-pharmacological strategies to address DOMS, focusing on evidence-based methods. These methods include massage, exercise, nutrition, and natural supplements. Research has shown that massage therapy enhances muscle recovery, exercise therapy reduces soreness, and nutrition therapy through protein and amino acid intake can alleviate DOMS. Furthermore, natural supplements like ginger, tart cherry juice, and curcumin have demonstrated the potential to reduce inflammation and manage DOMS.&#x0D; While pharmacological interventions may be considered for severe cases, the article underscores the importance of exercising caution due to potential side effects. In summary, DOMS management necessitates a holistic approach, combining multiple modalities and nutritional strategies to alleviate pain, enhance muscle recovery, and minimize the impact of this common condition on physically active individuals and athletes.

Treadmill training does not enhance skeletal muscle recovery following disuse atrophy in older male mice.

Introduction: A hallmark of aging is poor muscle recovery following disuse atrophy. Efficacious strategies to enhance muscle recovery following disuse atrophy in aging are non-existent. Prior exercise training could result in favorable muscle morphological and cellular adaptations that may promote muscle recovery in aging. Here, we characterized the impact of exercise training on skeletal muscle inflammatory and metabolic profiles and cellular remodeling and function, together with femoral artery reactivity prior to and following recovery from disuse atrophy in aged male mice. We hypothesized that 12 weeks of treadmill training in aged male mice would improve skeletal muscle cellular remodeling at baseline and during recovery from disuse atrophy, resulting in improved muscle regrowth. Methods: Physical performance, ex vivo muscle and vascular function, tissue and organ mass, hindlimb muscle cellular remodeling (macrophage, satellite cell, capillary, myofiber size, and fibrosis), and proteolytic, inflammatory, and metabolic muscle transcripts were evaluated in aged exercise-trained and sedentary mice. Results: We found that at baseline following exercise training (vs. sedentary mice), exercise capacity and physical function increased, fat mass decreased, and endothelial function improved. However, exercise training did not alter tibialis anterior or gastrocnemius muscle transcriptional profile, macrophage, satellite cell, capillarity or collagen content, or myofiber size and only tended to increase tibialis mass during recovery from disuse atrophy. Conclusion: While exercise training in old male mice improved endothelial function, physical performance, and whole-body tissue composition as anticipated, 12 weeks of treadmill training had limited impact on skeletal muscle remodeling at baseline or in response to recovery following disuse atrophy.

Hispidin-enriched Sanghuangporus sanghuang mycelia SS-MN4 ameliorate disuse atrophy while improving muscle endurance.

Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID-19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance. The effects of Sanghuangporus sanghuang SS-MN4 mycelia were tested on two groups of 6-week-old male mice-one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub-groups: a control group, a group that underwent hind limb casting for 7days and then recovered for 7days and a group that was administered with SS-MN4 orally for 14days, underwent hind limb casting for 7days and then recovered for 7days. The fatigue group was divided into two sub-groups: a control group that received no SS-MN4 intervention and an experimental group that was administered with SS-MN4 orally for 39days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA-seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS-MN4 treatment. In a disuse atrophy model induced by hind limb casting, supplementing with 250mg/kg of SS-MN4 for 14days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill (P<0.05). In a fatigue animal model, equivalent SS-MN4 dosage improved swimming (178.7%) and running (162.4%) activities (P<0.05) and reduced blood urea nitrogen levels by 18% (P<0.05). SS-MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA-seq and western blot studies from the C2C12 myotube showed that SS-MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage. Supplementation of SS-MN4 (250-mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast-twitch fibre regrowth and fatigue resistance.

Effect of Localized Vibration Massage on Popliteal Blood Flow.

There is a broad scope of literature investigating whole-body vibration (WBV) effects on blood flow (BF). However, it is unclear how therapeutic localized vibrations alter BF. Low-frequency massage guns are advertised to enhance muscle recovery, which may be through BF changes; however, studies using these devices are lacking. Thus, the purpose of this study was to determine if popliteal artery BF increases from localized vibration to the calf. Twenty-six healthy, recreationally active university students (fourteen males, twelve females, mean age 22.3 years) participated. Each subject received eight therapeutic conditions randomized on different days with ultrasound blood flow measurements. The eight conditions combined either control, 30 Hz, 38 Hz, or 47 Hz for a duration of 5 or 10 min. BF measurements of mean blood velocity, arterial diameter, volume flow, and heart rate were measured. Using a cell means mixed model, we found that both control conditions resulted in decreased BF and that both 38 Hz and 47 Hz resulted in significant increases in volume flow and mean blood velocity, which remained elevated longer than the BF induced by 30 Hz. This study demonstrates localized vibrations at 38 Hz and 47 Hz significantly increase BF without affecting the heart rate and may support muscle recovery.

Hesperidin Functions as an Ergogenic Aid by Increasing Endothelial Function and Decreasing Exercise-Induced Oxidative Stress and Inflammation, Thereby Contributing to Improved Exercise Performance.

The regulation of blood flow to peripheral muscles is crucial for proper skeletal muscle functioning and exercise performance. During exercise, increased mitochondrial oxidative phosphorylation leads to increased electron leakage and consequently induces an increase in ROS formation, contributing to DNA, lipid, and protein damage. Moreover, exercise may increase blood- and intramuscular inflammatory factors leading to a deterioration in endurance performance. The aim of this review is to investigate the potential mechanisms through which the polyphenol hesperidin could lead to enhanced exercise performance, namely improved endothelial function, reduced exercise-induced oxidative stress, and inflammation. We selected in vivo RCTs, animal studies, and in vitro studies in which hesperidin, its aglycone form hesperetin, hesperetin-metabolites, or orange juice are supplemented at any dosage and where the parameters related to endothelial function, oxidative stress, and/or inflammation have been measured. The results collected in this review show that hesperidin improves endothelial function (via increased NO availability), inhibits ROS production, decreases production and plasma levels of pro-inflammatory markers, and improves anaerobic exercise outcomes (e.g., power, speed, energy). For elite and recreational athletes, hesperidin could be used as an ergogenic aid to enhance muscle recovery between training sessions, optimize oxygen and nutrient supplies to the muscles, and improve anaerobic performance.

MicroRNA cargo of extracellular vesicles released by skeletal muscle fibro-adipogenic progenitor cells is significantly altered with disuse atrophy and IL-1β deficiency.

Fibro-adipogenic progenitor cells (FAPs) are a population of stem cells in skeletal muscle that play multiple roles in muscle repair and regeneration through their complex secretome; however, it is not well understood how the FAP secretome is altered with muscle disuse atrophy. Previous work suggests that the inflammatory cytokine IL-1β is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1β secretion are also known to stimulate the release of extracellular vesicles (EVs). Here, we examined the microRNA (miRNA) cargo of FAP-derived, platelet-derived growth factor receptor A (PDGFRα+) EVs from hindlimb muscles of wild-type and IL-1β KO mice after 14 days of single-hindlimb immobilization. Hindlimb muscles were isolated from mice following the immobilization period, and PDGFRα+ extracellular vesicles were isolated using size-exclusion chromatography and immunoprecipitation. Microarrays were performed to detect changes in miRNAs with unloading and IL-1β deficiency. Results indicate that the PDGFRα+, FAP-derived EVs show a significant increase in miRNAs, such as miR-let-7c, miR-let-7b, miR-181a, and miR-124. These miRNAs have previously been demonstrated to play important roles in cellular senescence and muscle atrophy. Furthermore, the expression of these same miRNAs was not significantly altered in FAP-derived EVs isolated from the immobilized IL-1β KO. These data suggest that disuse-related activation of IL-1β can mediate the miRNA cargo of FAP-derived EVs, contributing directly to the release of senescence- and atrophy-related miRNAs. Therapies targeting FAPs in settings associated with muscle disuse atrophy may therefore have the potential to preserve muscle function and enhance muscle recovery.

Mechanotherapy does not Enhance Recovery Following Muscle Disuse Atrophy in Female Rats

BackgroundRecovery from skeletal muscle atrophy is important for regaining function. We previously showed that mechanotherapy enhances regrowth of muscle in adult male rats by elevating protein synthesis.ObjectiveThe purpose of this study was to determine if female rats also respond to mechanotherapy during regrowth after disuse‐induced atrophy.HypothesisMechanotherapy in female rats augments muscle regrowth after atrophy by enhancing protein synthesis.MethodsAdult (10 month) F344/BN female rats were randomly assigned to one of four groups: weight‐bearing (WB; N=6), hindlimb suspension (HS; N=9), reambulation after HS without mechanotherapy (RA; N=9), or RA with mechanotherapy (RAM; N=10). HS lasted for 14 and RA for 7 days. Starting the day of RA, mechanotherapy was applied to the right gastrocnemius muscle at a load of 4.5N for 30 minutes every other day (4 bouts total). Rats received deuterium oxide (D2O) for determination of myofibrillar protein and RNA synthesis (Ksyn) and degradation (Kdeg). We analyzed gastrocnemius muscles for myonuclear number (dystrophin‐DAPI), satellite cell (SC) number (Pax7), and fiber type and cross‐sectional area (CSA; laminin‐myosin heavy chain). We used a one‐way ANOVA to determine statistical significance at p&lt;0.05. Values are mean ± SD.ResultsMuscle wet weight (g) was lower with HS (933 ± 56) compared to WB (1140 ± 86) and greater in RA (1012 ± 64) and RAM (1030 ± 41) compared to HS. However, no difference was observed between RA and RAM. Mean fiber CSA (µm2) was significantly lower in HS (1877 ± 244) compared to WB (2395 ± 248), while RA (2124 ± 287) was not different from WB or HS. RAM CSA (2013 ± 182) was lower than WB and not different from HS or RA. Myofibrillar Ksyn (mg/day) was lower in HS (13 ± 2.1) compared to WB (22 ± 2.2). RA (32 ± 3.2) and RAM (30 ± 4.3) were higher than HS and WB, but no difference was observed between RA and RAM. Myofibrillar Kdeg (1/t) was greater in HS (0.03 ± 0.004) compared to WB (0.02 ± 0.005), and RA (0.04 ± 0.007) and RAM (0.04 ± 0.005) were higher than HS and WB, but not different from each other. RNA Ksyn (%/day) was not different between WB (2 ± 0.2) and HS (2 ± 0.3), whereas RE (3 ± 0.4) and REM (4 ± 0.6) were both higher that WB and HS, but not different from each other. There were no differences in fiber type distribution between the groups. CSA of all fiber types was lower with HS, whereas no differences were observed between RA, RAM and HS. We did not find a significant difference in myonuclear number or centrally located nuclei between the groups. The number of SCs (per/fiber) was lower in HS (0.03 ± 0.01) and RA (0.04 ± 0.01) compared to WB (0.05 ± 0.008) and was higher in RAM (0.05 ± 0.02) compared to HS.ConclusionMuscle recovery from atrophy in female rats occurs with reambulation and elevated protein turnover is the underlying anabolic mechanism. We therefore conclude that the additional load using mechanotherapy does not enhance muscle recovery in females, which is different than the response previously published for males.

Impact of varying doses of omega-3 supplementation on muscle damage and recovery after eccentric resistance exercise

BackgroundExercise-induced muscle damage (EIMD) commonly occurs following intense resistance exercise and is associated with decrements in exercise performance and delayed muscle recovery. Thus, practical methods to attenuate EIMD would prove useful to both training and athletic populations. Omega-3 (n-3) supplementation has been shown to mitigate EIMD with evidence of increasing efficacy at higher doses (up to 6 g/day). However, data of its efficacy in trained individuals is limited. Therefore, this study investigated the effects of 6 and 8 g of n-3 supplementation on markers of muscle damage and muscle recovery after eccentric resistance exercise in resistance-trained males. MethodsUsing a double-blind, randomized, placebo-controlled design, 26 resistance trained males (23 ± 4 years; 173.6 ± 20.5 cm; 81.9 ± 9.7 kg; 14.2 ± 3.7% body fat) supplemented with 6 (n=10) or 8 g (n=7) of n-3 polyunsaturated fatty acids, or placebo (n=9) for 33 days. On day 30, participants performed a lower body muscle-damaging eccentric resistance exercise bout. Measures of muscle performance, soreness, and damage were taken pre-exercise on day 30 as well as on days 31–33, including vertical jump height (VJH), perceived muscle soreness (PMS), hip and knee range of motion (ROM), repetitions to fatigue (RTF) at 70% 1-RM, and serum creatine kinase (CK) while participants continued to supplement until day 33. ResultsThere were significant differences in VJH, PMS, and serum CK following the muscle-damaging exercise bout compared to pre-exercise (p<0.05). However, there were no significant (p>0.05) differences between supplementation groups (6 g, 8 g, and placebo) at any time point post-exercise (day 31–33). There were no changes in hip and knee ROM or RTF at any time point or between groups. Vertical jump height and PMS returned to pre-exercise levels despite CK remaining elevated post-exercise. ConclusionsThirty-three days of 6 and 8 g of n-3 supplementation did not attenuate EIMD or enhance muscle recovery following muscle-damaging eccentric resistance exercise in resistance-trained males. Further research using various n-3 supplementation durations, doses, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations may be needed to establish its efficacy in attenuating EIMD, which may vary between trained and untrained individuals. Furthermore, while circulating CK is commonly used to assess muscle damage, elevated CK levels may not reflect muscle recovery status following muscle-damaging exercise.

Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.

Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22-24 months) underwent 14days of hindlimb unloading (HU) followed by 7 or 14days of reloading (7 or 14days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.

PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging.

Impaired muscle recovery (size and strength) following a disuse period commonly occurs in older adults. Many of these individuals are not able to adequately exercise due to pain and logistic barriers. Thus, nutritional and pharmacological therapeutics, that are translatable, are needed to promote muscle recovery following disuse in older individuals. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be a suitable therapeutic target due to pleiotropic regulation of skeletal muscle. This review focuses on nutritional and pharmacological interventions that target PGC-1α and related Sirtuin 1 (SIRT1) and 5′ AMP-activated protein kinase (AMPKα) signaling in muscle and thus may be rapidly translated to prevent muscle disuse atrophy and promote recovery. In this review, we present several therapeutics that target PGC-1α in skeletal muscle such as leucine, β-hydroxy-β-methylbuyrate (HMB), arginine, resveratrol, metformin and combination therapies that may have future application to conditions of disuse and recovery in humans.

Viral vector delivery of follistatin enhances recovery of reinnervated muscle.

Poor recovery following nerve repair is due to progressive temporal loss of muscle function. Follistatin (FS), a glycoprotein with anabolic properties, may enhance muscle recovery following reinnervation. Seventy-two male Sprague-Dawley rats underwent temporary (3 or 6 month) denervation or sham denervation. After reinnervation, rats were administered adeno-associated viral vectors expressing FS deoxyribonucleic acid (isoform FS-317) injected into the target muscle or sham treatment. Final assessment included muscle function testing, muscle histomorphology, nerve histomorphology, and FS protein quantification. FS improved muscle mass and type IIB muscle fiber size, and increased G-ratios and mean axon diameter in the 6-month temporary denervation group (P < .05). Elevated FS protein levels were detected in treated muscle (P < .05). FS increased satellite cell counts following temporary denervation and repair (P < .05). FS treatment had anabolic, neurotrophic, and satellite cell stimulatory effects when administered following prolonged (6-month) temporary denervation and repair.