Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disorder, with accumulating evidence indicating metabolic disruptions in the skeletal muscle preceding disease symptoms, rather than them manifesting as a secondary consequence of motor neuron (MN) degeneration. Hence, energy homeostasis is deeply implicated in the complex physiopathology of ALS and skeletal muscle has emerged as a key therapeutic target. Here, we describe intrinsic abnormalities in ALS skeletal muscle, both in patient-derived muscle cells and in muscle cell lines with genetic knockdown of genes related to familial ALS, such as TARDBP (TDP-43) and FUS. We found a functional impairment of myogenesis that parallels defects of glucose oxidation in ALS muscle cells. We identified FOXO1 transcription factor as a key mediator of these metabolic and functional features in ALS muscle, via gene expression profiling and biochemical surveys in TDP-43 and FUS-silenced muscle progenitors. Strikingly, inhibition of FOXO1 mitigated the impaired myogenesis in both the genetically modified and the primary ALS myoblasts. In addition, specific in vivo conditional knockdown of TDP-43 or FUS orthologs (TBPH or caz) in Drosophila muscle precursor cells resulted in decreased innervation and profound dysfunction of motor nerve terminals and neuromuscular synapses, accompanied by motor abnormalities and reduced lifespan. Remarkably, these phenotypes were partially corrected by foxo inhibition, bolstering the potential pharmacological management of muscle intrinsic abnormalities associated with ALS. The findings demonstrate an intrinsic muscle dysfunction in ALS, which can be modulated by targeting FOXO factors, paving the way for novel therapeutic approaches that focus on the skeletal muscle as complementary target tissue.

Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarization.

AIMS: Study of the role of mitochondria-generated reactive oxygen species (mtROS) and mitochondrial polarization in mitochondrial fragmentation at the initial stages of myogenesis. MAIN METHODS: Mitochondrial morphology, Drp1 protein phosphorylation, mitochondrial electron transport chain components content, mtROS and mitochondrial lipid peroxidation levels, and mitochondrial polarization were evaluated on days 1 and 2 of human MB135 myoblasts differentiation. A mitochondria-targeted antioxidant SkQ1 was used to elucidate the effect of mtROS on mitochondria. KEY FINDINGS: In immortalized human MB135 myoblasts, mitochondrial fragmentation began on day 1 of differentiation before the myoblast fusion. This fragmentation was preceded by dephosphorylation of p-Drp1 (Ser-637). On day 2, an increase in the content of some mitochondrial proteins was observed, indicating mitochondrial biogenesis stimulation. Furthermore, we found that myogenic differentiation, even on day 1, was accompanied both by an increased production of mtROS, and lipid peroxidation of the inner mitochondrial membrane. SkQ1 blocked these effects and partially reduced the level of mitochondrial fragmentation, but did not affect the dephosphorylation of p-Drp1 (Ser-637). Importantly, mitochondrial fragmentation at early stages of MB135 differentiation was not accompanied by depolarization, as an important stimulus for mitochondrial fragmentation. SIGNIFICANCE: Mitochondrial fragmentation during early myogenic differentiation depends on mtROS production rather than mitochondrial depolarization. SkQ1 only partially inhibited mitochondrial fragmentation, without significant effects on mitophagy or early myogenic differentiation.

Inhibition of Sesn2 has negative regulatory effects on the myogenic differentiation of C2C12 myoblasts.

Sestrin2 (Sesn2) has been previously confirmed to be a stress-response molecule. However, the influence of Sesn2 on myogenic differentiation remains elusive. This study was conducted to analyze the role of Sesn2 in the myogenic differentiation of C2C12 myoblasts and related aspects in mdx mice, an animal model of Duchenne muscular dystrophy (DMD). Our results showed that knockdown of Sesn2 reduced the myogenic differentiation capacity of C2C12 myoblasts. Predictive analysis from two databases suggested that miR-182-5p is a potential regulator of Sesn2. Further experimental validation revealed that overexpression of miR-182-5p decreased both the protein and mRNA levels of Sesn2 and inhibited myogenesis of C2C12 myoblasts. These findings suggest that miR-182-5p negatively regulates myogenesis by repressing Sesn2 expression. Extending to an in vivo model of DMD, knockdown of Sesn2 led to decreased Myogenin (Myog) expression and increased Pax7 expression, while its overexpression upregulated Myog levels and enhanced the proportion of slow-switch myofibers. These findings indicate the crucial role of Sesn2 in promoting myogenic differentiation and skeletal muscle regeneration, providing potential therapeutic targets for muscular dystrophy.

Muscle cell-derived Ccl8 is a negative regulator of skeletal muscle regeneration.

Skeletal muscles undergo robust regeneration upon injury, and infiltrating immune cells play a major role in not only clearing damaged tissues but also regulating the myogenic process through secreted cytokines. Chemokine C-C motif ligand 8 (Ccl8), along with Ccl2 and Ccl7, has been reported to mediate inflammatory responses to suppress muscle regeneration. Ccl8 is also expressed by muscle cells, but a role of the muscle cell-derived Ccl8 in myogenesis has not been reported. In this study, we found that knockdown of Ccl8, but not Ccl2 or Ccl7, led to increased differentiation of C2C12 myoblasts. Analysis of existing single-cell transcriptomic datasets revealed that both immune cells and muscle stem cells (MuSCs) in regenerating muscles express Ccl8, with the expression by MuSCs at a much lower level, and that the temporal patterns of Ccl8 expression were different in MuSCs and macrophages. To probe a function of muscle cell-derived Ccl8 in vivo, we utilized a mouse system in which Cas9 was expressed in Pax7+ myogenic progenitor cells (MPCs) and Ccl8 gene editing was induced by AAV9-delivered sgRNA. Depletion of Ccl8 in Pax7+ MPCs resulted in accelerated muscle regeneration after barium chloride-induced injury in both young and middle-aged mice, and intramuscular administration of a recombinant Ccl8 reversed the phenotype. Accelerated regeneration was also observed when Ccl8 was depleted in Myf5+ or MyoD+ MPCs by similar approaches. Our results suggest that muscle cell-derived Ccl8 plays a unique role in regulating the initiation of myogenic differentiation during injury-induced muscle regeneration.

Unveiling the role of circRBBP7 in myoblast proliferation and differentiation: A novel regulator of muscle development.

Muscle development is a multistep process regulated by diverse gene networks, and circRNAs are considered novel regulators mediating myogenesis. Here, we systematically analyzed the role and underlying regulatory mechanisms of circRBBP7 in myoblast proliferation and differentiation. Results showed that circRBBP7 has a typical circular structure and encodes a 13 -kDa protein. By performing circRBBP7 overexpression and RNA interference, we found that the function of circRBBP7 was positively correlated with the proliferation and differentiation of myoblasts. Using RNA sequencing, we identified 1633 and 532 differentially expressed genes (DEGs) during myoblast proliferation or differentiation, respectively. The DEGs were found mainly enriched in cell cycle- and skeletal muscle development-related pathways, such as the MDM2/p53 and PI3K-Akt signaling pathways. Further co-IP and IF co-localization analysis revealed that VEGFR-1 is a target of circRBBP7 in myoblasts. qRT-PCR and WB analysis further confirmed the positive correlation between VEGFR-1 and circRBBP7. Moreover, we found that in vivo transfection of circRBBP7 into injured muscle tissues significantly promoted the regeneration and repair of myofibers in mice. Therefore, we speculate that circRBBP7 may affect the activity of MDM2 by targeting VEGFR-1, altering the expression of muscle development-related genes by mediating p53 degradation, and ultimately promoting myoblast development and muscle regeneration. This study provides essential evidence that circRBBP7 can serve as a potential target for myogenesis regulation and a reference for the application of circRBBP7 in cattle genetic breeding and muscle injury treatment.

Impaired myoblast differentiation and muscle IGF-1 receptor signaling pathway activation after N-glycosylation inhibition.

The role of N-glycosylation in the myogenic process remains poorly understood. Here, we evaluated the impact of N-glycosylation inhibition by Tunicamycin (TUN) or by phosphomannomutase 2 (PMM2) gene knockdown, which encodes an enzyme essential for catalyzing an early step of the N-glycosylation pathway, on C2C12 myoblast differentiation. The effect of chronic treatment with TUN on tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of WT and MLC/mIgf-1 transgenic mice, which overexpress muscle Igf-1Ea mRNA isoform, was also investigated. TUN-treated and PMM2 knockdown C2C12 cells showed reduced ConA, PHA-L, and AAL lectin binding and increased ER-stress-related gene expression (Chop and Hspa5 mRNAs and s/uXbp1 ratio) compared to controls. Myogenic markers (MyoD, myogenin, and Mrf4 mRNAs and MF20 protein) and myotube formation were reduced in both TUN-treated and PMM2 knockdown C2C12 cells. Body and TA weight of WT and MLC/mIgf-1 mice were not modified by TUN treatment, while lectin binding slightly decreased in the TA muscle of WT (ConA and AAL) and MLC/mIgf-1 (ConA) mice. The ER-stress-related gene expression did not change in the TA muscle of WT and MLC/mIgf-1 mice after TUN treatment. TUN treatment decreased myogenin mRNA and increased atrogen-1 mRNA, particularly in the TA muscle of WT mice. Finally, the IGF-1 production and IGF1R signaling pathways activation were reduced due to N-glycosylation inhibition in TA and EDL muscles. Decreased IGF1R expression was found in TUN-treated C2C12 myoblasts which was associated with lower IGF-1-induced IGF1R, AKT, and ERK1/2 phosphorylation compared to CTR cells. Chronic TUN-challenge models can help to elucidate the molecular mechanisms through which diseases associated with aberrant N-glycosylation, such as Congenital Disorders of Glycosylation (CDG), affect muscle and other tissue functions.

Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration.

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.

Developmental dynamics of mitochondrial fission and fusion proteins in functionally divergent skeletal muscles of goat.

During skeletal muscle development, the intricate mitochondrial network formation relies on continuous fission and fusion. This process in larger mammals differs from rodents, the most used animal models. However, the expression pattern of proteins regulating mitochondrial dynamics in developing skeletal muscle remains unexplored in larger mammals. Therefore, we characterized the cellular expression and tissue-level distribution of these proteins during development taking goat as a model. We have performed histological and immunohistochemical analyses to study metabolic features in various muscles. Neonatal muscles display uniform distribution of mitochondrial activity. In contrast, adult muscles exhibit clear distinctions based on their function, whether dedicated for posture maintenance or facilitating locomotion. Mitochondrial fission proteins like DRP-1, MFF, and fusion proteins like MFN-1 and 2 are abundantly expressed in neonatal muscles. Fission proteins exhibit drastic downregulation with limited peripheral expression, whereas fusion proteins continue to express in a fiber-specific manner during adulthood. Locomotory muscles exhibit different fibers based on mitochondrial activity and peripheralization with high SDH activity. The proximity ligation assay between MFN1 and MFN2 demonstrates that their interaction is restricted to subsarcolemmal mitochondria in adult fibers while distributed evenly in neonatal fibers. These differences between postural and locomotory muscles suggest their physiological and metabolic properties are different.

Unlocking the Nexus of Sirtuins: A Comprehensive Review of Their Role in Skeletal Muscle Metabolism, Development, and Disorders.

The sirtuins constitute a group of histone deacetylases reliant on NAD+ for their activity that have gained recognition for their critical roles as regulators of numerous biological processes. These enzymes have various functions in skeletal muscle biology, including development, metabolism, and the body's response to disease. This comprehensive review seeks to clarify sirtuins' complex role in skeletal muscle metabolism, including glucose uptake, fatty acid oxidation, mitochondrial dynamics, autophagy regulation, and exercise adaptations. It also examines their critical roles in developing skeletal muscle, including myogenesis, the determination of muscle fiber type, regeneration, and hypertrophic responses. Moreover, it sheds light on the therapeutic potential of sirtuins by examining their impact on a range of skeletal muscle disorders. By integrating findings from various studies, this review outlines the context of sirtuin-mediated regulation in skeletal muscle, highlighting their importance and possible consequences for health and disease.

Isolation of a persistently quiescent muscle satellite cell population.

Although studies have identified characteristics of quiescent satellite cells (SCs), their isolation has been hampered by the fact that the isolation procedures result in the activation of these cells into their rapidly proliferating progeny (myoblasts). Thus, the use of myoblasts for therapeutic (regenerative medicine) or industrial applications (cellular agriculture) has been impeded by the limited proliferative and differentiative capacity of these myogenic progenitors. Here we identify a subpopulation of satellite cells isolated from mouse skeletal muscle using flow cytometry that is highly Pax7-positive, exhibit a very slow proliferation rate (7.7 ± 1.2 days/doubling), and are capable of being maintained in culture for at least 3 mo without a change in phenotype. These cells can be activated from quiescence using a p38 inhibitor or by exposure to freeze-thaw cycles. Once activated, these cells proliferate rapidly (22.7 ± 0.2 h/doubling), have reduced Pax7 expression (threefold decrease in Pax7 fluorescence vs. quiescence), and differentiate into myotubes with a high efficiency. Furthermore, these cells withstand freeze-thawing readily without a significant loss of viability (83.1 ± 2.1% live). The results presented here provide researchers with a method to isolate quiescent satellite cells, allowing for more detailed examinations of the factors affecting satellite cell quiescence/activation and providing a cell source that has a unique potential in the regenerative medicine and cellular agriculture fields.NEW & NOTEWORTHY We provide a method to isolate quiescent satellite cells from skeletal muscle. These cells are highly Pax7-positive, exhibit a very slow proliferation rate, and are capable of being maintained in culture for months without a change in phenotype. The use of these cells by muscle researchers will allow for more detailed examinations of the factors affecting satellite cell quiescence/activation and provide a novel cell source for the regenerative medicine and cellular agriculture fields.

MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion.

Myogenesis is a multistep process that requires a spatiotemporal regulation of cell events resulting finally in myoblast fusion into multinucleated myotubes. Most major insights into the mechanisms underlying fusion seem to be conserved from insects to mammals and include the formation of podosome-like protrusions (PLPs) that exert a driving force toward the founder cell. However, the machinery that governs this process remains poorly understood. In this study, we demonstrate that MTM1 is the main enzyme responsible for the production of phosphatidylinositol 5-phosphate, which in turn fuels PI5P 4-kinase α to produce a minor and functional pool of phosphatidylinositol 4,5-bisphosphate that concentrates in PLPs containing the scaffolding protein Tks5, Dynamin-2, and the fusogenic protein Myomaker. Collectively, our data reveal a functional crosstalk between a PI-phosphatase and a PI-kinase in the regulation of PLP formation.

Efficacy of Split Versus Full-Body Resistance Training on Strength and Muscle Growth: A Systematic Review With Meta-Analysis.

ABSTRACT: Ramos-Campo, DJ, Benito-Peinado, PJ, Caravaca, LA, Rojo-Tirado, MA, and Rubio-Arias, JÁ. Efficacy of split versus full-body resistance training on strength and muscle growth: a systematic review with meta-analysis. J Strength Cond Res 38(7): 1330-1340, 2024-No previous study has systematically compared the effect of 2 resistance training routines commonly used to increase muscle mass and strength (i.e., split [Sp] and full-body [FB] routines). Our objective was to conduct a systematic review and meta-analysis following PRISMA guidelines to compare the effects on strength gains and muscle growth in healthy adults. 14 studies (392 subjects) that compared Sp and FB routines in terms of strength adaptations and muscle growth were included. Regarding the effects of the Sp or FB routine on both bench press and lower limbs strength, the magnitude of the change produced by both routines was similar (bench press: mean difference [MD] = 1.19; [-1.28, 3.65]; p = 0.34; k = 14; lower limb: MD = 2.47; [-2.11, 7.05]; p = 0.29; k = 14). Concerning the effect of the Sp vs. FB routine on muscle growth, similar effects were observed after both routines in the cross-sectional area of the elbow extensors (MD = 0.30; [-2.65, 3.24]; p = 0.84; k = 4), elbow flexors (MD = 0.17; [-2.54, 2.88]; p = 0.91; k = 5), vastus lateralis (MD = -0.08; [-1.82, 1.66]; p = 0.93; k = 5), or lean body mass (MD = -0.07; [-1.59, 1.44]; p = 0.92; k = 6). In conclusion, the present systematic review and meta-analysis provides solid evidence that the use of Sp or FB routines within a resistance training program does not significantly impact either strength gains or muscle hypertrophy when volume is equated. Consequently, individuals are free to confidently select a resistance training routine based on their personal preferences.

Regulation of myogenic cell proliferation and differentiation during mammalian skeletal myogenesis.

Mammalian skeletal myogenesis is a complex process that allows precise control of myogenic cells' proliferation, differentiation, and fusion to form multinucleated, contractile, and functional muscle fibers. Typically, myogenic progenitors continue growth and division until acquiring a differentiated state, which then permanently leaves the cell cycle and enters terminal differentiation. These processes have been intensively studied using the skeletal muscle developing models in vitro and in vivo, uncovering a complex cellular intrinsic network during mammalian skeletal myogenesis containing transcription factors, translation factors, extracellular matrix, metabolites, and mechano-sensors. Examining the events and how they are knitted together will better understand skeletal myogenesis's molecular basis. This review describes various regulatory mechanisms and recent advances in myogenic cell proliferation and differentiation during mammalian skeletal myogenesis. We focus on significant cell cycle regulators, myogenic factors, and chromatin regulators impacting the coordination of the cell proliferation versus differentiation decision, which will better clarify the complex signaling underlying skeletal myogenesis.

Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.

Human-induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno-free and robust methods for lineage-specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high-efficiency muscle lineage generation. HS conjugation to the C-terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.

Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration.

The function of many organs, including skeletal muscle, depends on their three-dimensional structure. Muscle regeneration therefore requires not only reestablishment of myofibers but also restoration of tissue architecture. Resident muscle stem cells (SCs) are essential for regeneration, but how SCs regenerate muscle architecture is largely unknown. We address this problem using genetic labeling of mouse SCs and whole-mount imaging to reconstruct, in three dimensions, muscle regeneration. Unexpectedly, we found that myofibers form via two distinct phases of fusion and the residual basement membrane of necrotic myofibers is critical for promoting fusion and orienting regenerated myofibers. Furthermore, the centralized myonuclei characteristic of regenerated myofibers are associated with myofibrillogenesis and endure months post injury. Finally, we elucidate two cellular mechanisms for the formation of branched myofibers, a pathology characteristic of diseased muscle. We provide a synthesis of the cellular events of regeneration and show that these differ from those used during development.

Echinacoside stimulates myogenesis and ATP-dependent thermogenesis in the skeletal muscle via the activation of D1-like dopaminergic receptors.

Recent studies have shown that some natural compounds from plants prevent obesity and related disorders, including the loss of skeletal muscle mass and strength. In this study, we investigated the effect of echinacoside (ECH), a caffeic acid glycoside from the phenylpropanoid class, on myogenesis and ATP-dependent thermogenesis in the skeletal muscle and its interaction with the dopaminergic receptors 1 and 5 (DRD1 and DRD5). We applied RT-PCR, immunoblot analysis, a staining method, and an assay kit to determine the effects of ECH on diverse target genes and proteins involved in skeletal muscle myogenesis and ATP-consuming futile processes. Our study demonstrated that ECH enhanced myogenic differentiation, glucose, and fatty acid uptake, as well as lipid catabolism, and induced ATP-dependent thermogenesis in vitro and in vivo. Moreover, ECH upregulated mitochondrial biogenesis proteins, mitochondrial oxidative phosphorylation (OXPHOS) complexes, and intracellular Ca2+ signaling as well as thermogenic proteins. These findings were further elucidated by mechanistic studies which showed that ECH mediates myogenesis via the DRD1/5 in C2C12 muscle cells. In addition, ECH stimulates α1-AR-mediated ATP-dependent thermogenesis via the DRD1/5/cAMP/SLN/SERCA1a pathway in C2C12 muscle cells. To the best of our knowledge, this is the first report that demonstrates the myogenic and thermogenic potential of ECH activity through the dopaminergic receptors. Understanding the novel functions of ECH in terms of its ability to prevent skeletal muscle loss and energy expenditure via ATP-consuming futile processes could help to develop potential alternative strategies to address muscle-related diseases, including combating obesity.

Entrenamiento de la fuerza en niños y adolescentes: Una Revisión sistemática años 2018-2022 / Strength training in children and adolescents: A systematic review years 2018-2022

Con el pasar del tiempo y especialmente en los últimos años el entrenamiento de la fuerza en niños y adolescentes ha venido tomando fuerza, convirtiéndose en uno de los componentes más importantes en el desarrollo de las capacidades físicas y motrices. El objetivo es Identificar las tendencias más recientes en lo referente a la prescripción del entrenamiento de la fuerza en niños y adolescentes la metodología: se desarrollo una revisión sistemática en la que fueron analizados 648 artículos de los cuales sólo 10 fueron seleccionados dada su relevancia y relación con el tema, además dichos artículos fueron extraídos de las bases de datos: Google Académico, Redalyc, Dialnet, y Scielo. En los resultados se pudo identificar en la revisión, (N=11) investigaciones experimentales cuantitativas y (N=15) estudios de revisión (cualitativas), así como un total de (n=234) participantes de ambos sexos en las intervenciones experimentales y un total de (n=139) estudios consultados en los artículos de revisión sistemática. En las conclusiones se logró identificar que el entrenamiento con pesos libres, y peso corporal son la tendencia más usada a la hora de prescribir entrenamiento de la fuerza. Consigo, se destaca que son los métodos de entrenamiento con pesas y bandas elásticas los implementos más utilizados para llevar a cabo su realización. La frecuencia recomendada es de 2 a 3 días por semana. El volumen que se destaca es de 2 a 3 series y 6 a 15 repeticiones por ejercicio donde la intensidad que prevalece son los porcentajes del 60% al 85% por ciento de 1RM o una intensidad moderada en la escala del esfuerzo percibido (AU)

With the passing of time and especially in recent years, strength training in children and adolescents has been gaining strength, becoming one of the most important components in physical and motor development. The objective is to identify the most recent trends regarding the prescription of strength training in children and adolescents. The methodology: a systematic review was developed in which 648 articles were analyzed, of which only 10 were selected given their relevance and relationship. with the subject, in addition said articles were extracted from the databases: Google Scholar, Redalyc, Dialnet, and Scielo. In the results it was possible to identify in the review, (N=11) quantitative experimental investigations and (N=15) review studies (qualitative), as well as a total of (n=234) participants of both sexes in the experimental interruptions and a total of (n=139) studies consulted in the systematic review articles. In the conclusions it will be identified that training with free weights and body weight are the most used trend when prescribing strength training. With it, it stands out that the methods of training with weights and elastic bands are the most used implements to carry out their realization. The recommended frequency is 2 to 3 days per week weeks. The volume that stands out is 2 to 3 sets and 6 to 15 repetitions per exercise where the prevailing intensity is 60% to 85% percent of 1RM or moderate intensity on the perceived exertion scale (AU)

Excess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.

The cellular prion protein (PrPC) is required for skeletal muscle function. Here, we report that a higher level of PrPC accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrPC inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation. PrPC selectively binds to a subset of miRNAs during myoblast differentiation, and the colocalization of PrPC and miR-214-3p was observed in the skeletal muscle of six myopathy patients with excessive PrPC. We demonstrate that PrPC is overexpressed in skeletal muscle cells under pathological conditions, inhibits muscle cell differentiation by physically interacting with a subset of miRNAs, and selectively recruits these miRNAs into its phase-separated condensate in living myoblasts, which in turn enhances liquid-liquid phase separation of PrPC, promotes pathological aggregation of PrP, and results in the inhibition of autophagy-related protein 5-dependent autophagy and muscle bundle formation in myopathy patients characterized by incomplete muscle regeneration.

Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors.

In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.

Humans contains around 650 skeletal muscles which allow the body to move around and maintain its posture. Skeletal muscles are made up of individual cells that bundle together into highly organized structures. If this group of muscles fail to develop correctly in the embryo and/or fetus, this can lead to muscular disorders that can make it painful and difficult to move. One way to better understand how skeletal muscles are formed, and how this process can go wrong, is to grow them in the laboratory. This can be achieved using induced pluripotent stem cells (iPSCs), human adult cells that have been 'reprogrammed' to behave like cells in the embryo that can develop in to almost any cell in the body. The iPSCs can then be converted into specific cell types in the laboratory, including the cells that make up skeletal muscle. Here, Mavrommatis et al. created a protocol for developing iPSCs into three-dimensional organoids which resemble how cells of the skeletal muscle look and arrange themselves in the fetus. To form the skeletal muscle organoid, Mavrommatis et al. treated iPSCs that were growing in a three-dimensional environment with various factors that are found early on in development. This caused the iPSCs to organize themselves in to embryonic and fetal structures that will eventually give rise to the parts of the body that contain skeletal muscle, such as the limbs. Within the organoid were cells that produced Pax7, a protein commonly found in myogenic progenitors that specifically mature into skeletal muscle cells in the fetus. Pax 7 is also present in 'satellite cells' that help to regrow damaged skeletal muscle in adults. Indeed, Mavrommatis et al. found that the myogenic progenitors produced by the organoid were able to regenerate muscle when transplanted in to adult mice. These findings suggest that this organoid protocol can generate cells that will give rise to skeletal muscle. In the future, these lab-grown progenitors could potentially be created from cells isolated from patients and used to repair muscle injuries. The organoid model could also provide new insights in to how skeletal muscles develop in the fetus, and how genetic mutations linked with muscular disorders disrupt this process.