Search Results (46)

Background/Objectives: Neurological impairments in children with Cerebral Palsy (CP) often lead to altered muscle architecture and function, resulting in calf muscle contractures. Orthotic immobilization aims to promote muscle–tendon unit lengthening through sustained stretch but may also induce disuse atrophy. This study investigated whether combining immobilization with daily activity yields different effects on muscle strength and gait function compared with immobilization alone. Methods: Fourteen ambulant children with spastic CP and equinus deformity (8 unilateral, 6 bilateral; mean age 9.93 ± 3.0 years; GMFCS I: 10, GMFCS II: 4) participated in a 12-week randomized controlled trial. Participants were assigned to either continuous immobilization (23 h/day) using a dynamic ankle–foot orthosis or a combined protocol consisting of 14 h/day immobilization and 10 h/day of activity involving ankle mobility and calf muscle activation. Outcomes included isometric muscle strength, joint range of motion, gait parameters, and functional measures (Gait Outcomes Assessment List (GOAL) and the Paediatric Outcome Data Collection Instrument (PODCI)). Data were analyzed using linear mixed models with Bonferroni correction. Results: Significant time effects were observed for the knee angle at initial contact (IC), the ankle angle at IC, maximum dorsiflexion, and maximum dorsiflexion during swing. A significant group × time interaction was found only for hindfoot-tibia angle at IC. Within-group improvements were noted in activities of daily living, body image and self-esteem, and basic mobility. No significant changes were found for muscle strength or for most questionnaire subscales. Conclusions: The findings indicate time-related improvements in gait, with no consistent advantage of the combined intervention. Further studies with larger samples are needed to evaluate potential long-term effects. Full article

Excessive alcohol consumption promotes clinical myopathy and injury-related immobilization. Because both alcohol and disuse jeopardize muscle health, their combined effects may synergistically accelerate fiber type-dependent muscle wasting. Ten-week-old male C57BL/6J mice were fed a control or 5% alcohol-diet for 3 weeks (NIAAA-model), with or without 1 week of unilateral hindlimb immobilization, generating four sets of limb muscles (n = 9/grp): control (CO), with immobilization (CI), alcohol (AL), with immobilization (AI). Gastrocnemius and soleus muscles were atrophied by CI, AL, and AI, whereas quadriceps atrophy was induced by CI and AI only (all p < 0.05). In soleus, CI, AL, and AL decreased p-mTOR (~40–60%, p < 0.01) and p-p70S6K (~50–87%, p < 0.05), indicating suppressed anabolic signaling. In contrast, in the quadriceps, alcohol increased p-4EBP1 by ~200% (p < 0.01), while p-Akt was elevated by ~180%, only in AI (p < 0.01). Myogenesis signaling was inhibited by alcohol and immobilization. For protein degradation, immobilization increased MAFbx by >50% in both muscles (p < 0.01). Quadriceps exhibited increased p-PERK (+53%) under AI (p < 0.05), whereas several markers of ER stress were reduced by all interventions in soleus (p < 0.05). These findings suggest that alcohol consumption does not exacerbate immobilization-induced atrophy; however, alcohol suppresses anabolic signaling in soleus, suggesting greater susceptibility to myopathy. Full article

Disuse-induced muscle atrophy (DMA), commonly resulting from immobilization, is driven by chronic inflammation and oxidative stress, which disrupts the balance between protein synthesis and degradation. Quinic acid (QA), a natural compound with known antioxidant and anti-inflammatory properties, was investigated for its potential to counteract muscle atrophy. Using a DMA-induced immobilization model in male C57BL/6N (8 weeks) mice, we found that oral QA administration significantly restored the weight and cross-sectional area of atrophic muscles and improved muscle function, as measured by grip strength and treadmill performance. QA also reduced the expression of pro-inflammatory cytokines (Tnf, Il6, and Myostatin) and E3 ubiquitin ligases (Trim63 and Fbxo32), while increasing antioxidant enzyme levels and serum IL-15 in DMA. In tumor necrosis factor-α-stimulated L6 myotubes, QA reversed inflammation- and oxidative stress-induced gene changes, suppressed NF-ĸB activation, and downregulated protein degradation pathways mediated by FoxO3α. Furthermore, QA restored the expression of myogenesis-related genes and reactivated PI3K/Akt and mTOR/p70S6K/4EBP1 signaling pathways, enhancing protein synthesis. Collectively, our findings demonstrate that QA mitigates immobilization-induced muscle atrophy by modulating inflammation, oxidative stress, and key anabolic and catabolic signaling pathways. These results suggest that QA is a promising functional compound for preserving skeletal muscle health under conditions of disuse. Full article

Long-term spaceflight induces multisystem stress, including cardiovascular deconditioning, skeletal muscle atrophy, immune suppression, and neuro-ocular syndromes. Current countermeasures reduce symptoms but cannot replicate the synergistic resilience needed for extended missions or critical illness. Hibernating animals, specifically brown bears (Ursus arctos), survive prolonged immobility, starvation, and bradycardia without resultant pathology. This review incorporates adaptations observed in bears and certain torpid species, including reversible insulin resistance, suppression of muscle atrophy genes MuRF1 and Atrogin-1, and maintenance of the heart despite seasonal production decline. The thirteen-lined ground squirrels (Ictidomys tridecemlineatus) maintain retinal structure and synaptic stability throughout torpor, avoiding neuro-ocular complications despite prolonged inactivity. Mechanisms span from RBM3-dependent synaptic maintenance, titin isoform remodeling under the control of RBM20, mTOR and FOXO pathway regulation, remodeled hydrogen sulfide metabolism, and microbiome-mediated nitrogen salvage. These adaptations are different from human adaptation to microgravity and disuse and offer translational candidates for synthetic torpor, probiotic engineering, neuroprotection, and protein-sparing therapy. Hibernators are not passive stress subjects; they perform coordinated anticipatory responses in multiple organs. Comparing these systems in large and small hibernators, we aim to uncover a biologically realistic path to human resilience. These findings guide a shift from reactive, pharmacological measures for preserving human health during space flight, intensive care, and extreme environments towards proactive, biologically initiated measures. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

Disused muscle atrophy (DMA) is characterized by skeletal muscle loss and functional decline due to prolonged inactivity. Though evidence remains limited, recent studies suggest that ferroptosis, an iron-dependent, lipid peroxidation-driven form of cell death, may contribute to DMA. Taurine, a natural amino acid enriched in energy drinks, can improve the proliferation and myogenic differentiation potential of myoblasts. This study aimed to investigate whether taurine supplementation could protect against DMA and explore its potential role in modulating ferroptosis. Using a hindlimb suspension-induced DMA model in male C57BL/6J mice (6–8 weeks old), we assessed muscle mass, function, ferroptosis-related markers, histopathological changes, and metabolic alterations. The results showed that taurine supplementation improved muscle strength and morphology while attenuating markers of ferroptosis, including iron accumulation, lipid peroxidation, and glutathione and related protein (NRF2, GPX4, and xCT) depletion. Metabolomic analysis suggested that taurine modulates disorders in glutathione and lipid metabolism, potentially associated with the regulation of the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 pathways. While these findings support a protective role for taurine and a possible link between ferroptosis and DMA, further functional studies are needed to confirm causality and assess the compound’s translational potential. This study provides initial in vivo evidence implicating ferroptosis in DMA and highlights taurine as a promising candidate for future therapeutic exploration. Full article

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet combined with aerobic exercise in hindlimb-unloaded mice on muscle fiber remodeling and metabolic adaptation. Methods: Seven-week-old male C57BL/6J mice were randomly divided into six groups: normal diet control (NC), normal diet with hindlimb unloading (NH), normal diet with hindlimb unloading and exercise (NHE), ketogenic diet control (KC), ketogenic diet with hindlimb unloading (KH), and ketogenic diet with hindlimb unloading and exercise (KHE). During the last two weeks of intervention, hindlimb unloading was applied to simulate microgravity. Aerobic exercise groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, and 6 days/week) for 8 weeks. Body weight, blood ketone, and glucose levels were measured weekly. Post-intervention assessments included the respiratory exchange ratio (RER), exhaustive exercise performance tests, and biochemical analyses of blood metabolic parameters. The skeletal muscle fiber-type composition was evaluated via immunofluorescence staining, lipid deposition was assessed using Oil Red O staining, glycogen content was analyzed by Periodic Acid–Schiff (PAS) staining, and gene expression was quantified using quantitative real-time PCR (RT-qPCR). Results: Hindlimb unloading significantly decreased body weight, induced muscle atrophy, and reduced exercise endurance in mice. However, the combination of KD and aerobic exercise significantly attenuated these adverse effects, as evidenced by increased proportions of oxidative muscle fibers (MyHC-I) and decreased proportions of glycolytic fibers (MyHC-IIb). Additionally, this combined intervention upregulated the expression of lipid metabolism-associated genes, including CPT-1b, HADH, PGC-1α, and FGF21, enhancing lipid metabolism and ketone utilization. These metabolic adaptations corresponded with improved exercise performance, demonstrated by the increased time to exhaustion in the KHE group compared to other hindlimb unloading groups. Conclusions: The combination of a ketogenic diet and aerobic exercise effectively ameliorates simulated microgravity-induced skeletal muscle atrophy and endurance impairment, primarily by promoting a fiber-type transition from MyHC-IIb to MyHC-I and enhancing lipid metabolism gene expression (CPT-1b, HADH, and PGC-1α). These findings underscore the potential therapeutic value of combined dietary and exercise interventions for mitigating muscle atrophy under simulated microgravity conditions. Full article

Hemojuvelin (HJV) is a membrane-bound protein prominently expressed in the skeletal muscle, heart, and liver. Despite its established function in iron regulation, the specific role of HJV in muscle physiology and pathophysiology is not well understood. In this study, we explored the involvement of HJV in disuse-induced muscle atrophy and uncovered the potential mechanisms. Hindlimb unloading (HU) resulted in soleus muscle atrophy in wild type (WT) mice, accompanied by a significant decrease in HJV protein expression. The muscle-specific deletion of Hjv (MKO) exacerbated myofiber atrophy, which was associated with an increase in the expression of muscle ubiquitin ligases following HU. Furthermore, the expression of transforming growth factor-β type II receptor (TβRII) and the level of phosphorylated Smad3 (p-Smad3) were elevated after HU, and these effects were exacerbated in MKO mice. The knockdown of TβRII in the skeletal muscle of MKO mice mitigated myofiber atrophy and reversed the hyperactivation of the TβRII/Smad3 pathway induced by HU. Our findings demonstrate that the absence of HJV contributes to the activation of the TβRII/Smad3 signaling pathway and, consequently, the onset of myofiber atrophy in response to HU. Given its abundant expression in skeletal muscle, HJV emerges as a potential therapeutic target for muscle atrophy. Full article

Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particularly from the perspective of the myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with the MS2 name) that were differentially expressed between the hindlimb unloading group and the control group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, as well as pathways like histidine, taurine, and hypotaurine metabolism, were linked to muscle atrophy. Protein and metabolism joint analyses revealed that some pathways, such as glutathione metabolism, ferroptosis, and lysosome pathways, were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analyses. The upregulation of proteins that are expressed in fast-twitch fibers indicates the conversion of slow-twitch fibers to fast-twitch fibers under hindlimb unloading. In addition, some differentially abundant metabolites and pathways revealed the important role of metabolism in muscle atrophy of the soleus. As shown in the graphical abstract, our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating proteomics and metabolomics of the soleus muscles. Full article

Chronic neuromuscular inactivity induces capillary regression within skeletal muscle. The objective of this study was to investigate the potential effects of dietary nucleic acids in counteracting the capillary reduction linked to chronic neuromuscular inactivity in the soleus muscle. The study utilized four distinct groups of female Wistar rats: a control group (CON), a hindlimb-unloading group (HU), an HU group supplemented with DNA (HU + DNA), and an HU group supplemented with RNA (HU + RNA). For a duration of two weeks, rats in the HU + DNA and HU + RNA groups were administered 1500 mg/kg of DNA or RNA orally on a daily basis. Two weeks of hindlimb unloading was concomitant with a reduction in the absolute weight of the soleus muscle and the capillary-to-fiber (C/F) ratio. This was associated with changes due to disuse, including increased accumulation of reactive oxygen species (ROS) and reduced levels of superoxide dismutase (SOD-2), along with elevated levels of thrombospondin-1 (TSP-1), an anti-angiogenic factor. Administering DNA at a medium concentration in the diet did not effectively prevent the reduction in the ratio between capillaries and fibers. In contrast, the equivalent concentration of RNA successfully averted the regression of capillaries during the unloading phase. Additionally, reactive oxygen species (ROS), superoxide dismutase-2 (SOD-2), and thrombospondin-1 (TSP-1) protein were kept at the same levels as in the control. The aforementioned findings reveal that RNA is more effective than DNA in preventing capillary regression triggered by muscle atrophy. Full article

Background: The clinical evaluation for disuse muscle atrophy usually depends on qualitative rating indicators with subjective judgments of doctors and some invasive measurement methods such as needle electromyography. Surface electromyography, as a non-invasive method, has been widely used in the detection of muscular and neurological diseases in recent years. In this paper, we explore how to evaluate disuse muscle atrophy based on surface electromyography; Methods: Firstly, we conducted rat experiments using hind-limb suspension to create a model of disuse muscle atrophy. Five groups of rats were suspended for 0, 3, 7, 14, and 21 days, respectively. We induced leg electromyography of rats through electrical stimulation and used fluorescence staining to obtain the fiber-type composition of rats’ leg muscles. We obtained the best-fitting frequency bands of power spectrum density of surface electromyography for type I and type II fibers in rats’ leg muscles by changing the frequency band boundaries. Secondly, we conducted tests on the human body and collected the electromyography of the atrophied muscles of the subjects over a period of 21 days. The changes in muscle fiber composition were evaluated using the frequency bands of power spectrum density obtained from rat experiments. The method was to evaluate the changes in type I fibers by the changes in the area of the best-fitting frequency band of type I fibers and to evaluate the changes in type II fibers by the changes in the area of the best-fitting frequency band of type II fibers. Results: The results of rat experiments showed that type I fibers best fit the frequency band of 20–330 Hz and type II fibers best fit the frequency band of 176–500 Hz. The results of human testing showed that the atrophy of the two types of fibers was consistent with the changes in the areas of the corresponding best-fitting frequency bands. Conclusions: The test results demonstrate the feasibility of using surface electromyography to evaluate muscle fiber-type composition and subsequently assess muscle atrophy. Further research may contribute to the diagnosis and treatment of disuse muscle atrophy. Full article

The prevalence of skeletal muscle atrophy, caused by disease and aging, is rising as life expectancy increases. Exercise is the most effective treatment option; however, it is often impractical for individuals suffering from disease or bedridden. The formulation of non-exercise-based interventions is necessary. This study assessed the impact of acupuncture (AC), electro-acupuncture (EA), and electrical stimulation (ES) on muscle mass and contractile properties in a model of casting-induced muscle atrophy. Sprague-Dawley rats (n = 40) were assigned to five groups: control (CON), cast (CT), cast receiving AC (CT-AC), cast receiving EA (CT-EA), and cast receiving ES (CT-ES) (n = 8 each). Treatments were 15 min and three times/week for 14 days. Contractile properties and protein markers of atrophy and inflammation were measured. Casting decreased muscle mass and fiber cross-sectional area, but AC, EA, and ES attenuated cast-induced muscle atrophy. All treatments increased peak twitch tension compared to CT. CT increased the protein levels of MAFbx and MuRF1, while AC, EA, and ES mitigated the elevation of these proteins. Our results indicate that acupuncture, electro-acupuncture, and electrical stimulation show promise as therapeutic strategies to counteract skeletal muscle loss and dysfunction resulting from disuse atrophy caused by injury, disease, and aging. Full article

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. Full article

Disuse muscle atrophy is a disease caused by restricted activity, affecting human health and animal protein quality. While extensive research on its mechanism has been studied in mammals, comparatively little is known about this process in chickens, which are a significant source of protein for human consumption worldwide. Understanding the mechanisms underlying skeletal muscle atrophy in chickens is crucial for improving poultry health and productivity, as well as for developing strategies to mitigate muscle loss. In this study, two groups of chickens were subjected to limb immobilization for two and four weeks, respectively, in order to induce disuse muscle atrophy and uniformly sampled gastrocnemius muscle at the fourth week. A combined analysis of the transcriptome and metabolome was conducted to investigate the mechanisms of disuse-induced muscle atrophy. Through H&E staining and immunofluorescence, we found that, compared to slow-twitch muscle fibers, the fast-twitch muscle fibers showed a greater reduction in cross-sectional area in the immobilized leg, and were also the main driver of changes in cross-sectional area observed in the non-immobilized leg. Integrated analysis revealed that differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly enriched in pathways related to energy metabolism, such as fatty acid metabolism, oxidative phosphorylation (OXPHOS), and glycolysis. These results provide important insights for further research on disuse muscle atrophy. Full article

Prolonged inactivity and disuse conditions, such as those experienced during spaceflight and prolonged bedrest, are frequently accompanied by detrimental effects on the motor system, including skeletal muscle atrophy and bone loss, which greatly increase the risk of osteoporosis and fractures. Moreover, the decrease in glucose and lipid utilization in skeletal muscles, a consequence of muscle atrophy, also contributes to the development of metabolic syndrome. Clarifying the mechanisms involved in disuse-induced musculoskeletal deterioration is important, providing therapeutic targets and a scientific foundation for the treatment of musculoskeletal disorders under disuse conditions. Skeletal muscle, as a powerful endocrine organ, participates in the regulation of physiological and biochemical functions of local or distal tissues and organs, including itself, in endocrine, autocrine, or paracrine manners. As a motor organ adjacent to muscle, bone tissue exhibits a relative lag in degenerative changes compared to skeletal muscle under disuse conditions. Based on this phenomenon, roles and mechanisms involved in the communication between skeletal muscle and bone, especially from muscle to bone, under disuse conditions have attracted widespread attention. In this review, we summarize the roles and regulatory mechanisms of muscle-derived myokines and extracellular vesicles (EVs) in the occurrence of muscle atrophy and bone loss under disuse conditions, as well as discuss future perspectives based on existing research. Full article