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Toll-like receptor 4 (TLR4) activation increases pro-inflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Exercise is recommended to reduce TLR4 expression and intracellular signaling, but the mechanisms for how this occurs are unknown, and even less is known regarding the effect of exercise on TLR4 expressed in skeletal muscle. Activation of TLR4 expressed on skeletal muscle can elicit local metabolic and atrophic effects in addition to systemic inflammation from TLR4 activation on immune cells. Therefore, the purpose of this dissertation project is to better uncover the nature and mechanisms by which exercise affects TLR4 expression and intracellular signaling in different cell types (peripheral blood mononuclear cells: PBMCs and skeletal muscle) using cell culture and human experiments. In this project, we showed that in an in vitro model of muscle contraction, repeated myotube contractions can prevent TLR4-mediated myotube atrophy, partially due to decreasing membrane-bound TLR4 and increasing soluble TLR4 (sTLR4). Next, we provided evidence that divergent mechanisms may regulate TLR4 expression on PBMCs by augmenting membrane-bound and soluble TLR4 expressions following workload-matched exercise in normoxic and hypoxic environments. Finally, we demonstrated that TLR4 receptor regulation and cellular signaling responses to vigorous exercise are dependent on training status (endurance-trained vs untrained) but not tissue type (PBMCs vs skeletal muscle). Together these studies provide a better understanding of TLR4 regulation in response to an acute bout of exercise in different tissue types and how endurance training may affect these responses.

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. Discu

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling pathway. Proteomic analysis of muscle cells subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensities of 5% and 2% as well as the control. Additionally, 10% SL suppressed RNA and protein synthesis while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with the highest expression in 2% SL. Further examination showed that the ADP/ATP ratio was increased after 10% SL compared to the control and that SL induced changes in mitochondrial biogenesis. Furthermore, Seahorse assay results indicate that 10% SL enhances mitochondrial respiration. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in muscle cells.

To date, the mechanisms that underlie skeletal muscle decline due to ageing remain unclear. A hypothesis known as the mitochondrial theory of ageing postulates that a loss of mitochondrial quality control (MQC) leads to an increase in mitochondrial dysfunction over lifespan. Consequently, this loss of MQC underpins the deterioration in quality and function of all tissues throughout the organism, including skeletal muscle. Aerobic exercise has been found to potently stimulate increases in mitochondrial function and has been found to also greatly benefit aged skeletal muscle quality and function, suggesting that exercise may be a powerful tool to mitigate aged related skeletal muscle mitochondrial decline. A primary aspect of mitochondrial quality control is known as mitophagy, which is defined as the selective removal and degradation of damaged or dysfunctional mitochondria from the mitochondrial reticulum. The inherently dynamic and transient nature of mitophagy has provided a significant methodological challenge to mitophagy research, with many previous studies having to rely upon semi-quantitative techniques as the sole measurement. Additionally, many studies have relied upon toxic mitochondrial uncoupler chemical agents to induce mitophagy which limit the investigative potential of such experiments. These difficulties have led to conflicting evidence as to how skeletal muscle mitophagy alters in the context of ageing, with no clear consensuses being reached to date. To overcome these limitations, the Mito-QC mitophagy reporter mouse model was developed to provide a robust and functional method to visualize and measure mitophagy in vivo. Therefore, the aim of this thesis was to employ the Mito-QC model to gain deeper insight into the mechanistic properties of skeletal muscle mitophagy under basal and exercised conditions, and to conclusively determine how mitophagy is altered due to the process of ageing. Under basal physiological conditions, it was found that the

The injuries received are accompanied by massive damage to the soft tissues of the limbs, main vessels and nerves, and the development of compartment syndrome. Violation of muscle function in the case of a limb injury can be both a consequence of denervation — as a result of damage to peripheral nerves, and ischemia with subsequent necrosis and fibrosis — as a result of direct or indirect damage to muscles, «tenotomy syndrome» — in case of traumatic damage to tendons and muscles yams, with the simultaneous combination of denervation and ischemia. Markers for assessing the state of muscle tissue — levels of Na+, K+ and Ca++ electrolytes, indicators of kidney function (urea, creatinine); glucose and the products of its transformations — lactate (lacticacid) and pyruvate (pyruvic acid) and, finally, muscle enzymes, namely creatine kinase (CK) and lactate dehydrogenase (LDH). Objective. To study the biochemical indicators of blood (activity of energy metabolism enzymes and electrolyte content) of military personnel with ischemic contracture and muscle denervation after a mine-explosive injury. Methods. The blood serum of 45 people, who were divided into IV groups, was analyzed. The average age of patients of the II group was 33.75 ± 3.46; III — 37 ± 3.66; IV — 35.86 ± 2.35. The results. The activity of LDH and CK and the content of electrolytes Na+, K+, Ca++ were determined in blood serum. Conclusions. LDH plays a key role in lactate metabolism and maintenance of energy balance in skeletal muscle. Its increased activity indicates the presence of hypoxia due to ischemic contracture of the limb and damage to peripheral nerves. KK enzyme protects cell membranes from damage. The tendency to decrease the activity of CC is a negative sign that reflects the initial process of destruction of the cell membranes of muscles damaged by a mine-explosive injury. The obtained results can be used to determine the severity of pathological processes in patients after traumatic damage to

Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions., Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.

Objectives Muscle function and size decline with age, but long-term effects of resistance training in older adults are largely unknown. Here, we explored the long-lasting (3 years) effects of 1 year of supervised resistance training with heavy loads. Methods The LIve active Successful Ageing (LISA) study was a parallel group randomised controlled trial at a university hospital in Denmark. Older adults (n=451) at retirement age were randomised to 1 year of heavy resistance training (HRT), moderate-intensity training (MIT) or a non-exercising control group (CON). Primary outcome measure was leg extensor power. Secondary outcomes included maximal isometric quadriceps torque (isometric leg strength) and body composition (dual-energy X-ray absorptiometry (DXA)). Participants completed test procedures at baseline, following the 1-year intervention, and 2 and 4 years post study start. Results At the 4-year assessment, 369 participants attended (mean age=71 years, 61% women). The main finding was that across all four time points, there was a significant group×time interaction in isometric leg strength (F6,1049=8.607, p<0.001, Embedded Image=0.05). Individuals in HRT maintained baseline performance in isometric leg strength (Baseline: 149.7±51.5 Nm, 4 years: 151.5±51.1 Nm, t(1050)=1.005, p=1.00) while participants in CON and MIT decreased. Conclusion In well-functioning older adults at retirement age, 1 year of HRT may induce long-lasting beneficial effects by preserving muscle function. Trial registration number NCT02123641., Objectives Muscle function and size decline with age, but long-term effects of resistance training in older adults are largely unknown. Here, we explored the long-lasting (3 years) effects of 1 year of supervised resistance training with heavy loads. Methods The LIve active Successful Ageing (LISA) study was a parallel group randomised controlled trial at a university hospital in Denmark. Older adults (n=451) at retirement age were randomised to 1 year of heavy resistance training (HRT), moderate-intensity training (MIT) or a non-exercising control group (CON). Primary outcome measure was leg extensor power. Secondary outcomes included maximal isometric quadriceps torque (isometric leg strength) and body composition (dual-energy X-ray absorptiometry (DXA)). Participants completed test procedures at baseline, following the 1-year intervention, and 2 and 4 years post study start. Results At the 4-year assessment, 369 participants attended (mean age=71 years, 61% women). The main finding was that across all four time points, there was a significant group×time interaction in isometric leg strength (F 6,1049 =8.607, p<0.001, n2=0.05). Individuals in HRT maintained baseline performance in isometric leg strength (Baseline: 149.7±51.5 Nm, 4 years: 151.5±51.1 Nm, t(1050)=1.005, p=1.00) while participants in CON and MIT decreased. Conclusion In well-functioning older adults at retirement age, 1 year of HRT may induce long-lasting beneficial effects by preserving muscle function. Trial registration number NCT02123641.

Reactive oxygen species (ROS) are well-established signaling molecules implicated in a wide range of cellular processes, including both oxidative stress and intracellular redox signaling. In the context of insulin action within its target tissues, ROS have been reported to exert both positive and negative regulatory effects. However, the precise molecular mechanisms underlying this duality remain unclear. This Review examines the complex role of ROS in insulin action, with a particular focus on skeletal muscle. We aim to address three critical aspects: (a) the proposed intracellular pro-oxidative redox shift elicited by insulin, (b) the evidence supporting that redox-sensitive cysteine modifications impact insulin signaling and action, and (c) cellular mechanisms underlying how ROS can paradoxically act as both enhancers and inhibitors of insulin action. This Review underscores the urgent need for more systematic research to identify specific reactive species, redox targets, and the physiological significance of redox signaling in maintaining insulin action and metabolic health, with a particular emphasis on human skeletal muscle.

Carey Fineman Ziter Syndrome (CFZS) is a rare autosomal recessive disease caused by mutations in the MYMK locus which encodes the protein, myomaker. Myomaker is essential for fusion and concurrent myonuclei donation of muscle progenitors during growth and development. Strikingly, in humans, MYMK mutations appear to prompt myofiber hypertrophy but paradoxically, induce generalised muscle weakness. As the underlying cellular mechanisms remain unexplored, the present study aimed to gain insights by combining myofiber deep-phenotyping and proteomic profiling. Hence, we isolated individual muscle fibers from CFZS patients and performed mechanical, 3D morphological and proteomic analyses. Myofibers from CFZS patients were ~ 4x larger than controls and possessed ~ 2x more myonuclei than those from healthy subjects, leading to disproportionally larger myonuclear domain volumes. These greater myonuclear domain sizes were accompanied by smaller intrinsic cellular force generating-capacities in myofibers from CFZS patients than in control muscle cells. Our complementary proteomic analyses indicated remodelling in 233 proteins particularly those associated with cellular respiration. Overall, our findings suggest that myomaker is somewhat functional in CFZS patients, but the associated nuclear accretion may ultimately lead to non-functional hypertrophy and altered energy-related mechanisms in CFZS patients. All of these are likely contributors of the muscle weakness experienced by CFZS patients.

Type 2 diabetes is preceded by a defective insulin response, yet our knowledge of the precise mechanisms is incomplete. Here, we investigate how insulin resistance alters skeletal muscle signaling and how exercise partially counteracts this effect. We measured parallel phenotypes and phosphoproteomes of insulin-resistant (IR) and insulin-sensitive (IS) men as they responded to exercise and insulin (n = 19, 114 biopsies), quantifying over 12,000 phosphopeptides in each biopsy. Insulin resistance involves selective and time-dependent alterations to signaling, including reduced insulin-stimulated mTORC1 and non-canonical signaling responses. Prior exercise promotes insulin sensitivity even in IR individuals by “priming” a portion of insulin signaling prior to insulin infusion. This includes MINDY1 S441, which we show is an AKT substrate. We found that MINDY1 knockdown enhances insulin-stimulated glucose uptake in rat myotubes. This work delineates the signaling alterations in IR skeletal muscle and identifies MINDY1 as a regulator of insulin action.

Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. Although AMP-activated protein kinase (AMPK), the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear. We found that AMPK directly inhibits NIX-dependent mitophagy by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 and an additional identified site, Ser694. By contrast, AMPK activation increases Parkin phosphorylation and enhances the rate of depolarization-induced mitophagy, independently of ULK1. We show that this happens both in cultured cells and tissues in vivo, using the mito-QC mouse model. Our work unveils a mechanism whereby AMPK activation downregulates mitophagy of functional mitochondria but enhances that of dysfunctional/damaged ones.

The heterogeneous fiber type composition of skeletal muscle makes it challenging to decipher the molecular signaling events driving the health- and performance benefits of exercise. We developed an optimized workflow for transcriptional profiling of individual human muscle fibers before, immediately after, and after 3 h of recovery from high-intensity interval cycling exercise. From a transcriptional point-of-view, we observe that there is no dichotomy in fiber activation, which could refer to a fiber being recruited or nonrecruited. Rather, the activation pattern displays a continuum with a more uniform response within fast versus slow fibers during the recovery from exercise. The transcriptome-wide response immediately after exercise is characterized by some distinct signatures for slow versus fast fibers, although the most exercise-responsive genes are common between the two fiber types. The temporal transcriptional waves further converge the gene signatures of both fiber types toward a more similar profile during the recovery from exercise. Furthermore, a large heterogeneity among all resting and exercised fibers was observed, with the principal drivers being independent of a slow/fast typology. This profound heterogeneity extends to distinct exercise responses of fibers beyond a classification based on myosin heavy chains. Collectively, our single-fiber methodological approach points to a substantial between-fiber diversity in muscle fiber responses to high-intensity interval exercise. NEW & NOTEWORTHY By development of a single-fiber transcriptomics technology, we assessed the transcriptional events in individual human skeletal muscle fibers upon high-intensity exercise. We demonstrate a large variability in transcriptional activation of fibers, with shared and distinct gene signatures for slow and fast fibers. The heterogeneous fiber-specific exercise response extends beyond this traditional slow/fast categorization. These findings expand on our unders

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. Di

Abstract: Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM. We first conducted in vitro experiments in isolated single myofibres from patients and found that Mavacamten successfully reversed the myosin ATP overconsumption. Following this, we assessed its short-term in vivo effects using the conditional nebulin knockout (cNeb KO) mouse model and subsequently performing global proteomics profiling in dissected soleus myofibres. After a 4 week treatment period, we observed a remodelling of a large number of proteins in both cNeb KO mice and their wild-type siblings. Nevertheless, these changes were not related to the energy proteome, indicating that short-term Mavacamten treatment is not sufficient to properly counterbalance the metabolically dysregulated proteome of cNeb KO mice. Taken together, our findings emphasize Mavacamten potency in vitro but challenge its short-term efficacy in vivo. (Figure presented.). Key points: No cure exists for nemaline myopathy, a type of genetic skeletal muscle disease mainly derived from mutations in genes encoding myofilament proteins. Applying Mavacamten, a small molecule directly targeting the myofilaments, to isolated membrane-permeabilized muscle fibres from human patients restored myosin energetic disturbances. Treating a mouse model of nemaline myopathy in vivo with Mavacamten for 4 weeks, remodelled the skeletal muscle fibre proteome without any noticeable effects on energetic proteins. Short-term Mavacamt

In cell biology, ribosomal RNA (rRNA) 2′O-methyl (2′-O-Me) is the most prevalent posttranscriptional chemical modification contributing to ribosome heterogeneity. The modification involves a family of small nucleolar RNAs (snoRNAs) and is specified by box C/D snoRNAs (SNORDs). Given the importance of ribosome biogenesis for skeletal muscle growth, we asked if rRNA 2′-O-Me in nascent ribosomes synthesized in response to a growth stimulus is an unrecognized mode of ribosome heterogeneity in muscle. To determine the pattern and dynamics of 2′-O-Me rRNA, we used a sequencing-based profiling method called RiboMeth-seq (RMS). We applied this method to tissue-derived rRNA of skeletal muscle and rRNA specifically from the muscle fiber using an inducible myofiber-specific RiboTag mouse in sedentary and mechanically overloaded conditions. These analyses were complemented by myonuclear-specific small RNA sequencing to profile SNORDs and link the rRNA epitranscriptome to known regulatory elements generated within the muscle fiber. We demonstrate for the first time that mechanical overload of skeletal muscle 1) induces decreased 2′-O-Me at a subset of skeletal muscle rRNA and 2) alters the SNORD profile in isolated myonuclei. These findings point to a transient diversification of the ribosome pool via 2′-O-Me during growth and adaptation in skeletal muscle. These findings suggest changes in ribosome heterogeneity at the 2′-O-Me level during muscle hypertrophy and lay the foundation for studies investigating the functional implications of these newly identified “growth-induced” ribosomes., In cell biology, ribosomal RNA (rRNA) 2′O-methyl (2′-O-Me) is the most prevalent posttranscriptional chemical modification contributing to ribosome heterogeneity. The modification involves a family of small nucleolar RNAs (snoRNAs) and is specified by box C/D snoRNAs (SNORDs). Given the importance of ribosome biogenesis for skeletal muscle growth, we asked if rRNA 2′-O-Me in nascent ribosomes synthesized in response to a growth stimulus is an unrecognized mode of ribosome heterogeneity in muscle. To determine the pattern and dynamics of 2′-O-Me rRNA, we used a sequencing-based profiling method called RiboMeth-seq (RMS). We applied this method to tissue-derived rRNA of skeletal muscle and rRNA specifically from the muscle fiber using an inducible myofiber-specific RiboTag mouse in sedentary and mechanically overloaded conditions. These analyses were complemented by myonuclear-specific small RNA sequencing to profile SNORDs and link the rRNA epitranscriptome to known regulatory elements generated within the muscle fiber. We demonstrate for the first time that mechanical overload of skeletal muscle 1) induces decreased 2′-O-Me at a subset of skeletal muscle rRNA and 2) alters the SNORD profile in isolated myonuclei. These findings point to a transient diversification of the ribosome pool via 2′-O-Me during growth and adaptation in skeletal muscle. These findings suggest changes in ribosome heterogeneity at the 2′-O-Me level during muscle hypertrophy and lay the foundation for studies investigating the functional implications of these newly identified “growth-induced” ribosomes.

Context: Housing temperature is a critical regulator of mouse metabolism and thermoneutral housing can improve model translation to humans. However, the impact of housing temperature on the ability of wheel running exercise training to rescue the detrimental effect of diet-induced obese mice is currently not fully understood. Objective: To investigate how housing temperature affects muscle metabolism in obese mice with regard to calcium handling and exercise training (ET) adaptations in skeletal muscle, and benefits of ET on adiposity and glucometabolic parameters. Methods: Lean or obese female mice were housed at standard ambient temperature (22 °C) or thermoneutrality (30 °C) with/without access to running wheels. The metabolic phenotype was investigated using glucose tolerance tests, indirect calorimetry, and body composition. Molecular muscle adaptations were measured using immunoblotting, qPCR, and spectrophotometric/fluorescent assays. Results: Obese female mice housed at 22 °C showed lower adiposity, lower circulating insulin levels, improved glucose tolerance, and elevated basal metabolic rate compared to 30 °C housing. Mice exposed to voluntary wheel running exhibited a larger fat loss and higher metabolic rate at 22 °C housing compared to thermoneutrality. In obese female mice, glucose tolerance improved after ET independent of housing temperature. Independent of diet and training, 22 °C housing increased skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) activity. Additionally, housing at 22 °C elevated the induction of training-responsive muscle proteins in obese mice. Conclusion: Our findings highlight that housing temperature significantly influences adiposity, insulin sensitivity, muscle physiology, and exercise adaptations in diet-induced obese female mice.

Striated muscle cells, encompassing cardiac myocytes and skeletal muscle fibers, are fundamental to athletic performance, facilitating blood circulation and coordinated movement through contraction. Despite their distinct functional roles, these muscle types exhibit similarities in cytoarchitecture, protein expression, and excitation-contraction coupling. Both muscle types also undergo molecular remodeling in energy metabolism and cell size in response to acute and repeated exercise stimuli to enhance exercise performance. Reactive oxygen species (ROS) produced by NADPH oxidase (NOX) isoforms 2 and 4 have emerged as signaling molecules that regulate exercise adaptations. This review systematically compares NOX2 and NOX4 expression, regulation, and roles in cardiac and skeletal muscle responses across exercise modalities. We highlight the many gaps in our knowledge and opportunities to let future skeletal muscle research into NOX-dependent mechanisms be inspired by cardiac muscle studies and vice versa. Understanding these processes could enhance the development of exercise routines to optimize human performance and health strategies that capitalize on the advantages of physical activity.

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole-body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic–euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose-stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2-fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men.

Work-related musculoskeletal disorders are increasingly prevalent and affect the health and performance of workers, especially in informal and rudimentary manufacturing sectors, which by their very nature, such as panel mills, involve repetitive movements, prolonged postures, and handling of loads, factors that predispose to dis-ergonomic risks and painful symptoms, leading to long-term occupational diseases and altered functionality. Objective: To determine the perceived symptomatology and dis-ergonomic risk among workers in a panela factory. Methodology: The study design was descriptive and cross-sectional. Twenty-nine workers of a panela mill in the municipality of Sandoná were evaluated, using the Nordic instrument for perceived symptomatology and the OWAS battery for dis-ergonomic risk. Results: 82.8% of participants had musculoskeletal discomfort; of this percentage, the body area with the greatest discomfort was the dorsal or lumbar region at 37.5%; 86.2% had dis-ergonomic risk. Conclusions: The results indicate that the population presented musculoskeletal symptomatology and that the manipulation of loads, together with forced postures, represent harmful effects to the workers of panela mills, given the characteristics of the work., Os distúrbios musculoesqueléticos relacionados ao trabalho são cada vez mais prevalentes e afetam a saúde e o desempenho dos trabalhadores, especialmente em setores de manufatura informais e rudimentares, que, por sua própria natureza, como os moinhos de panela, envolvem movimentos repetitivos, posturas prolongadas e manuseio de cargas, fatores que predispõem a riscos não ergonômicos e sintomas dolorosos, levando a doenças ocupacionais de longo prazo e alteração da funcionalidade. Objetivo: determinar a sintomatologia percebida e o risco dis-ergonômico entre os trabalhadores de uma fábrica de panelas. Metodologia: o desenho do estudo foi descritivo e transversal. Vinte e nove trabalhadores de uma fábrica de panela no município de Sandoná foram avaliados, usando o instrumento nórdico para sintomatologia percebida e a bateria OWAS para risco dis-ergonômico. Resultados: 82,8% dos participantes apresentaram desconforto musculoesquelético; dessa porcentagem, a área do corpo com maior desconforto foi a região dorsal ou lombar, com 37,5%; 86,2% apresentaram risco dis-ergonômico. Conclusões: os resultados indicam que a população apresentou sintomatologia musculoesquelética e que a manipulação de cargas, juntamente com as posturas forçadas, representa efeitos nocivos aos trabalhadores de moinhos de panela, dadas as características do trabalho., Los trastornos musculoesqueléticos relacionados con el trabajo son cada vez más frecuentes e impactan en la salud y por ende en el desempeño del trabajador, aún más cuando se trata de sectores productivos informales y rudimentarios que, por sus características, como los molinos paneleros, implican movimientos repetitivos, posturas prolongadas y manipulación de cargas, los cuales son factores que predisponen al riesgo disergonómico y a una sintomatología dolorosa en estos trabajadores, ocasionando enfermedades laborales a largo plazo y alteración de la funcionalidad. Objetivo: determinar la sintomatología sentida y riesgo disergonómico en trabajadores de un molino de panela. Metodología: el diseño del estudio fue de tipo descriptivo, transversal. Se evaluó a 29 trabajadores de un molino panelero en el municipio de Sandoná, se aplicó el instrumento nórdico para la sintomatología sentida y la batería OWAS para el riesgo disergonómico. Resultados: el 82,8 % de los participantes presentó molestias músculo esqueléticas y, de este porcentaje, la zona corporal de mayor molestia fue la región dorsal o lumbar con un 37,5 %; además, la población correspondiente al 86,2 % presenta riesgo disergonómico. Conclusión: los resultados indican que la población sí evidencia sintomatología músculo esquelética y que la manipulación de cargas junto con posturas forzadas representa efectos dañinos en los trabajadores de molinos de panela, dadas las características del trabajo.

Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.

Maintaining muscle mass is crucial for health and physical activity. Around age 40, muscle mass begins to decline, potentially leading to sarcopenia, a condition associated with frailty and increased fall risk. Age-related muscle loss is complex and multifactorial. The prevailing view is that this loss is driven by anabolic resistance, which is a reduced capacity to increase muscle protein synthesis (MPS) after anabolic cues, i.e., essential amino acids (EAA) or resistance exercise (REx). Mechanistically, this is thought to be underpinned by dysregulation of the mTORC1 signaling pathway. However, it is unclear whether anabolic resistance contributes to muscle loss in healthy, physically active older adults or if studies supporting this have been confounded by other factors, e.g., inactivity and adiposity. Aging also induces changes at the myocellular level, such as satellite cell loss and morphological alterations, but whether these changes are due to aging itself or lifestyle factors is still being debated. This thesis examined how anabolic cues impact MPS, mTORC1 signaling, and markers of protein degradation in young and older men. Emphasis was on performing analyses on whole muscle samples and in type I and type II fibers separately. Further aims were to investigate features of muscle fibers in young and older men, focusing on morphology, satellite cells, capillarization, and denervation-reinnervation cycles. The final aim was to develop a valid and fast method for fiber type identification of isolated fibers. In paper I, the MPS and mTORC1 signaling response was examined in young and older men after EAA intake alone and combined with REx. The results showed comparable rates of MPS across age groups in response to EAA intake, both alone and with REx. Additionally, mTORC1 signaling was similar to or more pronounced in older men compared to younger men. Notably, older men displayed higher levels of amino acid transporters, nutrient sensors, an, Det övergripande syftet med avhandlingen var att öka förståelsen för de cellulära och molekylära mekanismer som ligger bakom muskelförlust vid åldrande, med särskilt fokus på anabol resistens. Detta tillstånd kännetecknas av en nedsatt förmåga att stimulera proteinsyntesen vid anabola stimuli, såsom intag av proteinrik mat eller fysisk träning. En viktig bakomliggande faktor för anabol resistens är minskad aktivering av mTOR, en signalväg essentiell för cellens tillväxt. Vidare undersöktes hur åldrande påverkar egenskaperna hos snabba (typ II) och långsamma (typ I) muskelfibrer. I avhandlingen utvecklades också en ny metod för att förenkla framtida studier på enskilda muskelfibrer. Studierna omfattade friska, fysiskt aktiva, män i åldrarna 18–35 år och 65–74 år som genomförde ett styrketräningspass samt intog essentiella aminosyror (EAA). Muskelprover analyserades för proteinsyntes, mTOR-signalering och markörer för proteinnedbrytning. Ytterligare analyser i typ I och typ II muskelfibrer utfördes för att studera morfologi, stamceller, kapillärer och tecken på denervering för att öka förståelsen av åldrandets påverkan på dessa olika fibertyper. Resultatet från studie I visade att proteinsyntesen ökade efter intag av EAA, en effekt som förstärktes efter styrketräning, men inga skillnader fanns mellan unga och äldre män. Den äldre gruppen hade däremot högre mTOR-signalering och ökade nivåer av proteiner relaterade till aminosyraupptag och aktivering av mTOR-signalvägen. Studie II visade att äldre män hade en högre andel typ I fibrer, mindre och missformade typ II fibrer, samt färre stamceller och kapillärer kring typ II fibrerna. Den äldre gruppen hade också fler denerverade fibrer och en högre andel grupperade typ I fibrer. I studie III utvecklades en ny metod, THRIFTY, för snabb och effektiv fibertypning av enskilda muskelfibrer. Metoden möjliggjorde, bland annat, tillförlitlig identifiering av hybridfibrer. Studie IV visade att muskelfibrer frå

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.

Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition, and its accuracy may be influenced by various factors, including bladder filling. This study aims to investigate the impact of bladder filling on the accuracy of BIA measurements. An experimental crossover study was conducted with sedentary young adults. The influence of bladder filling on total body water (TBW), fat mass (FM), fat-free mass (FFM), and basal metabolic rate (BMR) was assessed. Participant in underwear followed an overnight fast. They were instructed to abstain from vigorous physical activity and alcohol for at least 24 h prior to the session. The results obtained from single-frequency and multi-frequency BIA devices were compared. The findings suggest that bladder filling does not affect measured impedance; however, changes in weight following bladder voiding influenced derived BIA results. Specifically, TBW, FM, and BMR values significantly reduced after voiding (p < 0.05). Furthermore, the study found poor agreement between single-frequency and multi-frequency BIA devices, indicating that they are not interchangeable. Bladder filling does affect BIA measurements, not clinically meaningful. Further research is needed to explore the implications of these findings for clinical practice and research protocols.

Introduction and objective: The sporting environment exposes the practitioner to frequent consumption of high doses of alcohol, generally after exercise, which can harm the physiological adaptations of muscle tissue, affecting the athlete's performance. Therefore, this study aims to evaluate, through a systematic review, the impact of alcohol consumption on muscle recovery in men after physical exercise. Materials and methods: This is a systematic review, carried out in August 2023, in the Pubmed and Lilacs databases. Clinical trials with male humans, published in Portuguese, English or Spanish, in the last ten years, corresponding to the period from 2013 to 2023, were included; addressing the relationship between alcohol consumption and muscle mass recovery in male athletes. The studies selected for the research used healthy and physically active adult males. Results: 397 articles were found and only three articles were listed for the systematic review. Ethanol consumption ranged from 0.88 to 1.5 g/kg of weight. The impact on skeletal muscle depends on the exercise and dose of alcohol. In general, acute alcohol ingestion after exercise does not affect power, strength and pain during recovery, but it reduces the rates of muscle protein synthesis, mTOR signaling, autophagy and mitochondrial biogenesis, impairing muscle adaptation and long-term performance. term . Conclusion: It is recommended caution with alcohol consumption after physical exercise, always seeking the necessary nutrients to promote adequate recovery., Introduzione e obiettivo: L'ambiente sportivo espone il praticante al consumo frequente di elevate dosi di alcol, generalmente dopo l'esercizio, che può essere dannoso per gli adattamenti fisiologici del tessuto muscolare, influenzando le prestazioni dell'atleta. Pertanto, questo studio si propone di valutare, attraverso una revisione sistematica, l’impatto del consumo di alcol sul recupero muscolare negli uomini dopo l’esercizio fisico. Materiali e metodi: si tratta di una revisione sistematica, effettuata nell'agosto 2023, nei database Pubmed e Lilacs. Sono stati inclusi studi clinici con esseri umani di sesso maschile, pubblicati in portoghese, inglese o spagnolo, negli ultimi dieci anni, corrispondenti al periodo dal 2013 al 2023; affrontare la relazione tra consumo di alcol e massa muscolare negli atleti di sesso maschile. Gli studi selezionati per la ricerca hanno utilizzato maschi adulti sani e fisicamente attivi. Risultati: sono stati trovati 397 articoli e di questi, solo tre articoli sono rimasti per la revisione sistematica. Il consumo di etanolo variava da 0,88 a 1,5 g/kg di peso. L’impatto sul muscolo scheletrico dipende dall’esercizio fisico e dalla dose di alcol. In generale, l’ingestione acuta di alcol dopo l’esercizio non influisce sulla potenza, sulla forza e sul dolore durante il recupero, ma riduce i tassi di sintesi proteica muscolare, la segnalazione mTOR, l’autofagia e la biogenesi mitocondriale, compromettendo l’adattamento muscolare e le prestazioni a lungo termine. Conclusione: si consiglia cautela nel consumo di alcol dopo l'esercizio fisico, cercando sempre i nutrienti necessari per favorire un adeguato recupero., Introdução e objetivo: O ambiente esportivo expõe o praticante a frequentes consumos de altas doses de álcool, geralmente após o exercício, o que pode ser prejudicial para as adaptações fisiológicas do tecido muscular, afetando o desempenho do atleta. Assim, este estudo visa avaliar através de uma revisão sistemática o impacto do consumo de álcool na recuperação muscular em homens após exercício físico. Materiais e métodos: Trata-se de uma revisão sistemática, realizada no período de agosto de 2023, nas bases de dados Pubmed e Lilacs. Foram incluídos ensaios clínicos com humanos do sexo masculino, publicados em português, inglês ou espanhol, nos últimos dez anos, correspondendo ao período de 2013 a 2023; abordando a relação entre o consumo de bebidas alcoólicas e massa muscular em atletas homens. Os estudos selecionados para a pesquisa utilizaram indivíduos adultos do sexo masculino, saudáveis e ativos fisicamente. Resultados: Foram encontrados 397 artigos e destes, permaneceram somente três artigos para a revisão sistemática. O consumo de etanol variou de 0,88 a 1,5 g/kg de peso. O impacto no músculo esquelético depende do exercício e da dose do álcool. Em geral, a ingestão aguda de álcool após o exercício não afeta a potência, força e dor na recuperação, porém reduz as taxas de síntese de proteínas musculares, sinalização de mTOR, autofagia e biogênese mitocondrial, prejudicando a adaptação muscular e o desempenho a longo prazo. Conclusão: Sugere-se prudência com o consumo de álcool após exercício físico, sempre buscando os nutrientes necessários para promover a recuperação adequada., Introducción y objetivo: El ambiente deportivo expone al practicante al consumo frecuente de altas dosis de alcohol, generalmente después del ejercicio, lo que puede ser perjudicial para las adaptaciones fisiológicas del tejido muscular, afectando el rendimiento del deportista. Por tanto, este estudio tiene como objetivo evaluar, a través de una revisión sistemática, el impacto del consumo de alcohol en la recuperación muscular en hombres después del ejercicio físico. Materiales y métodos: Se trata de una revisión sistemática, realizada en agosto de 2023, en las bases de datos Pubmed y Lilacs. Se incluyeron ensayos clínicos con humanos masculinos, publicados en portugués, inglés o español, en los últimos diez años, correspondientes al período de 2013 a 2023; abordar la relación entre el consumo de alcohol y la masa muscular en deportistas masculinos. Los estudios seleccionados para la investigación utilizaron hombres adultos sanos y físicamente activos. Resultados: Se encontraron 397 artículos y de estos, sólo tres artículos quedaron para la revisión sistemática. El consumo de etanol osciló entre 0,88 y 1,5 g/kg de peso. El impacto sobre el músculo esquelético depende del ejercicio y la dosis de alcohol. En general, la ingesta aguda de alcohol después del ejercicio no afecta la potencia, la fuerza y ​​el dolor durante la recuperación, pero reduce las tasas de síntesis de proteínas musculares, la señalización mTOR, la autofagia y la biogénesis mitocondrial, perjudicando la adaptación muscular y el rendimiento a largo plazo. Conclusión: Se sugiere precaución con el consumo de alcohol después del ejercicio físico, buscando siempre los nutrientes necesarios para favorecer una adecuada recuperación.

Stimulated contractions are shown to increase toll-like receptor 4 (TLR4) release from C2C12 myotubes in vitro. The purpose of this study was to determine if the release of TLR4 from myotubes is controlled by proteolytic membrane cleavage. A broad-spectrum metalloprotease inhibitor was used to test this hypothesis in a C2C12 cell culture model, and TLR4 concentrations in the cell culture supernatant were measured via enzyme-linked immunosorbent assay (ELISA) following stimulated myotube contractions. ELISA analysis revealed TLR4 concentrations below the sensitivity threshold of the ELISA kit for all experimental conditions. In confirming the effectiveness of the electrical pulse stimulation (EPS) treatment, ANOVA analysis showed myotube diameter was not significantly different between conditions (p > 0.05), and supernatant IL-6 concentrations were not increased with EPS treatment. These results reflect an abnormal response of the C2C12 myotubes to stimulated contractions here, and additional troubleshooting is needed to test the proposed hypothesis.

Background: Polycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead tochanges in protein levels and biological function. Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Results: Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Conclusions: Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective., CC BY 4.0 DEED5 January 2024Corresponding author: Anna Benrick, University of Gothenburg, Institute of Neuroscience and Physiology, Department of Physiology, Box 432, 405 30 Gothenburg, Sweden. Phone: +46 (0)709490148. E-mail: anna.benrick@gu.seFunding: A.B. holds funding from the Swedish Research Council (2020-02485), E.SV. holds funding from the Swedish Research Council (2022-00550), the Novo Nordisk Foundation (NNF22OC0072904), and I.W.A. holds funding from the Swedish Research Council (2020-01463), Mary von Sydow Foundation, Diabetes Wellness Sverige, and EFSD//European Research Programme on ‘New Targets for Diabetes or Obesity-related Metabolic Diseases’ supported by MSD 2022, and J.N. holds funding from IngaBritt and Arne Lundberg Research Foundation.Manuskript i medRxiv: DOI: 10.1101/2023.03.08.23286896

This work reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a magnetized polycaprolactone-based composite. In situ iron oxide nanoparticle deposition on oxidized graphene yields homogeneously dispersed magnetic particles with sizes above 0.5 µm and low aspect ratio, preventing cellular internalization and toxicity. With these fillers, homogeneous magnetic composites with high magnetic content (up to 20 weight %) are obtained and processed in a solvent-free manner for the first time. MEW of magnetic composites enabled the creation of skeletal muscle-inspired design of hexagonal scaffolds with tunable fiber diameter, reconfigurable modularity, and zonal distribution of magneto-active and nonactive material, with elastic tensile deformability. External magnetic fields below 300 mT are sufficient to trigger out-of-plane reversible deformation. In vitro culture of C2C12 myoblasts on three-dimensional (3D) Matrigel/collagen/MEW scaffolds showed that microfibers guided the formation of 3D myotube architectures, and the presence of magnetic particles does not significantly affect viability or differentiation rates after 8 days. Centimeter-sized skeletal muscle constructs allowed for reversible, continued, and dynamic magneto-mechanical stimulation. Overall, these innovative microfiber scaffolds provide magnetically deformable platforms suitable for dynamic culture of skeletal muscle, offering potential for in vitro disease modeling.