Adult Muscle Research Articles

RACK1 is evolutionary conserved in satellite stem cell activation and adult skeletal muscle regeneration

Skeletal muscle growth and regeneration involves the activity of resident adult stem cells, namely satellite cells (SC). Despite numerous mechanisms have been described, different signals are emerging as relevant in SC homeostasis. Here we demonstrated that the Receptor for Activated C-Kinase 1 (RACK1) is important in SC function. RACK1 was expressed transiently in the skeletal muscle of post-natal mice, being abundant in the early phase of muscle growth and almost disappearing in adult mature fibers. The presence of RACK1 in interstitial SC was also detected. After acute injury in muscle of both mouse and the fruit fly Drosophila melanogaster (used as alternative in vivo model) we found that RACK1 accumulated in regenerating fibers while it declined with the progression of repair process. To note, RACK1 also localized in the active SC that populate recovering tissue. The dynamics of RACK1 levels in isolated adult SC of mice, i.e., progressively high during differentiation and low compared to proliferating conditions, and RACK1 silencing indicated that RACK1 promotes both the formation of myotubes and the accretion of nascent myotubes. In Drosophila with depleted RACK1 in all muscle cells or, specifically, in SC lineage we observed a delayed recovery of skeletal muscle after physical damage as well as the low presence of active SC in the wound area. Our results also suggest the coupling of RACK1 to muscle unfolded protein response during SC activation. Collectively, we provided the first evidence that transient levels of the evolutionarily conserved factor RACK1 are critical for adult SC activation and proper skeletal muscle regeneration, favoring the efficient progression of SC from a committed to a fully differentiated state.

Influence of forward head posture on muscle activation pattern of the trapezius pars descendens muscle in young adults

Forward head posture (FHP) is a serious problem causing head and neck disability, but the characteristics of muscle activity during long-term postural maintenance are unclear. This study aimed to investigate a comparison of electromyography (EMG) activation properties and subjective fatigue between young adults with and without habitual FHP. In this study, we examined the changes in the spatial and temporal distribution patterns of muscle activity using high-density surface EMG (HD-SEMG) in addition to mean frequency, a conventional measure of muscle fatigue. Nineteen male participants were included in the study (FHP group (n = 9; age = 22.3 ± 1.5 years) and normal group (n = 10; age = 22.5 ± 1.4 years)). Participants held three head positions (e.g., forward, backward, and neutral positions) for a total of 30 min each, and the EMG activity of the trapezius pars descendens muscle during posture maintenance was measured by HD-SEMG. The root mean square (RMS), the modified entropy, and the correlation coefficient were calculated. Additionally, the visual analogue scale (VAS) was evaluated to assess subjective fatigue. The RMS, VAS, modified entropy, and correlation coefficients were significantly higher in the FHP group than in the normal group (p < 0.001). With increasing postural maintenance time, the modified entropy and correlation coefficient values significantly decreased, and the mean frequency and VAS values significantly increased (p < 0.001). Furthermore, the forward position had significantly higher RMS, correlation coefficient, modified entropy, and VAS values than in the neutral position (p < 0.001). The HD-SEMG potential distribution patterns in the FHP group showed less heterogeneity and greater muscle activity in the entire muscle and subjective fatigue than those in the normal group. Excess muscle activity even in the neutral/comfortable position in the FHP group could potentially be a mechanism of neuromuscular conditions in this population.

Inducible deletion of raptor and mTOR from adult skeletal muscle impairs muscle contractility and relaxation.

Skeletal muscle weakness has been associated with different pathological conditions, including sarcopenia and muscular dystrophy, and is accompanied by altered mammalian target of rapamycin (mTOR) signalling. We wanted to elucidate the functional role of mTOR in muscle contractility. Most loss-of-function studies for mTOR signalling have used the drug rapamycin to inhibit some of the signalling downstream of mTOR. However, given that rapamycin does not inhibit all mTOR signalling completely, we generated a double knockout for mTOR and for the scaffold protein of mTORC1, raptor, in skeletal muscle. We found that double knockout in mice results in a more severe phenotype compared with deletion of raptor or mTOR alone. Indeed, these animals display muscle weakness, increased fibre denervation and a slower muscle relaxation following tetanic stimulation. This is accompanied by a shift towards slow-twitch fibres and changes in the expression levels of calcium-related genes, such as Serca1 and Casq1. Double knockout mice show a decrease in calcium decay kinetics after tetanus in vivo, suggestive of a reduced calcium reuptake. In addition, RNA sequencing analysis revealed that many downregulated genes, such as Tcap and Fhod3, are linked to sarcomere organization. These results suggest a key role for mTOR signalling in maintaining proper fibre relaxation in skeletal muscle. KEY POINTS: Skeletal muscle wasting and weakness have been associated with different pathological conditions, including sarcopenia and muscular dystrophy, and are accompanied by altered mammalian target of rapamycin (mTOR) signalling. Mammalian target of rapamycin plays a crucial role in the maintenance of muscle mass and functionality. We found that the loss of both mTOR and raptor results in contractile abnormalities, with severe muscle weakness and delayed relaxation following tetanic stimulation. These results are associated with alterations in the expression of genes involved in sarcomere organization and calcium handling and with an impairment in calcium reuptake after contraction. Taken together, these results provide a mechanistic insight into the role of mTOR in muscle contractility.

Focal Myositis with CD8+T-Cell predominance: an Inflammatory Myositis Mimicking a Soft Tissue Neoplasm

Abstract Introduction/Objective FM is a rare self-limiting T-cell rich lesion arising within muscles of young adults as a solitary lesion and can be confused with a variety of neoplastic/inflammatory conditions or lymphoma. Here we describe a rare T-cell rich variant of FM with CD8 predominance. Methods/Case Report A 51-year-old female presented with two-month history of left trapezius swelling. MRI showed an enhancing tumor within the muscle, suspicious of sarcoma, less likely myeloma. Results (if a Case Study enter NA) Biopsy showed diffuse infiltration of small lymphocytes in a fibrotic background and atrophic skeletal muscle. These lymphocytes stained positive for CD2, CD3, CD7, CD8, CD5 (partial), TIA1 (partial), CD43, CD57 and negative for CD4, CD30, CD56, CD57, granzyme B, perforin, BCL-6, BCL-2, Pax5, TCL1, and CD56. Ki-67 was (&amp;lt;10%) with few background CD20+ B cells. By flow cytometry, the CD8+ T-cells co-express CD2, CD3, CD7, with dim CD5 expression. TCR gene rearrangement study by PCR showed no clonal TCR Gamma gene rearrangement. Conclusion FM is extremely rare with only 22 cases well-described in the literature, all predominantly composed of CD4+ T-cells, clinically concerning for low-grade sarcomas, as inflammatory myofibroblastic tumor, inflammatory leiomyosarcoma, or liposarcoma. Careful analysis is essential for correct diagnosis. Mimics include other causes of myositis, such as polymyositis and inclusion body myositis. Depending on the extent of lymphocytic infiltrate, gene rearrangement studies might be necessary to rule out clonality. Recognition of this rare entity with excellent prognosis is crucial to provide appropriate management and avoid unnecessary, aggressive procedures.

Metformin suppresses progression of muscle aging via activation of the AMP kinase-mediated pathways in Drosophila adults.

Metformin, a medicine used for the treatment of type 2 diabetes, was previously reported to suppress age-dependent hyperproliferation of intestinal stem cells in Drosophila. Here, we aimed to investigate its anti-aging effects on other tissues, such as adult muscle and elucidate the mechanisms underlying the anti-ageing effect. To evaluate the anti-muscle ageing effect of Metformin, we visualized ubiquitinated protein aggregates accumulated in adult muscle as the flies age by immunostaining and measured the total pixel size of the aggregates. We altered gene expression in the muscle by induction of dsRNA against the relevant mRNAs or mRNAs encoding the constitutively active mutant proteins using the Gal4/UAS system. We determined the mRNA levels by quantitative Real Time-Polymerase Chain Reaction (QRT-PCR). Continuous metformin feeding significantly extended the lifespan of Drosophila adults. Furthermore, the feeding suppressed the aging-dependent accumulation of ubiquitinated aggregates in adult muscle. To delineate the mechanism through which metformin influences the muscle aging phenotype, we induced the constitutively active AMPK specifically in the muscles and found that the activation of the AMPK-mediated pathway was sufficient for the anti-aging effect of Metformin. Furthermore, the AMPK-mediated downregulation of Tor-mediated pathways, subsequent induction of an eIF-4E inhibitor were involved in the effect. These genetic data suggested that the metformin effect is related to the partial suppression of protein synthesis in ribosomes. Furthermore, metformin stimulated autophagy induction in adult muscles. Our results suggest that metformin can be regarded as an anti-aging compound in Drosophila muscle. The stimulation of autophagy was also involved in the anti-aging effect, which delayed the progression of muscle aging in Drosophila adults.

OR24-1 Paracrine Growth Factor Signaling Regulates Muscle Regeneration in Aged Mice via microRNA 501

Abstract Background Skeletal muscle is one of to the most dynamic and plastic tissues. The capacity to regenerate arises from adult muscle stem cells termed myogenic progenitors (MPs) that are activated in response to injury and differentiate to replenish damaged muscle fibers. The age-related loss of muscle mass is reflected in the reduced regenerative potential of MPs. The underlying mechanisms are still unclear and insights into alterations in adult muscle stem cells during ageing are urgently needed. We have previously identified a novel muscle-specific microRNA, miR-501-3p, that is enriched in activated MPs. Pharmacological inhibition of miR-501 during muscle regeneration promoted small-diameter neofibers. Here, we provide evidence for the regulation of miR-501 in skeletal muscle during aging and its effect on newly formed myofibers using genetic deletion in mice. Methods We analysed the regulation and upstream signalling pathways of miR-501 in primary myoblasts from mice and humans and in skeletal muscle from young and aged mice. We generated a novel Cre-loxP mouse model, which allowed for global and MP-specific deletion of miR-501. Skeletal muscle regeneration was induced using cardiotoxin (CTX) and assessed using immunofluorescence and transcriptomic analysis. Results miR-501 was upregulated in muscle cells by the paracrine growth factors platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) through the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) signalling axis. Expression levels of miR-501 as well as its upstream regulators Pdgf and Vegf were significantly reduced in skeletal muscle from aged mice (22 months) compared to young mice (3 months) by 67.8% (p&amp;lt;0.001), 40.0% (p&amp;lt;0.01) and 36.3% (p&amp;lt;0.05), respectively. Genetic deletion of miR-501 in mice resulted in muscle fibers with decreased size in adult skeletal muscle and in newly formed myofibers during muscle regeneration. RNA-seq of regenerating muscle annotated a critical role for miR-501 in the organisation of muscle filaments. We identified a miR-501-dependent sarcomeric gene signature that involves genes such as myosin heavy chains, titin and tubulin polymerization-promoting protein. This was confirmed in vitro in myotubes from mice and humans in which miR-501 was deleted either genetically or pharmacologically using antagomirs. Altered sarcomeric gene expression correlated with an increased sarcomere length in myotubes lacking miR-501 (2.49 ± 0.08μm vs 3.22 ± 0.15μm, p&amp;lt;0.01). Conclusion Our data indicate that paracrine growth factor signalling contributes to muscle fiber formation via miR-501 in myogenic progenitor cells and its effect on the sarcomere. Restoring the Pdgf+Vegf/miR-501 axis might have the potential to improve muscle formation during aging. Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.

Manipulating the Resistance Training Volume in Middle-Aged and Older Adults: A Systematic Review with Meta-Analysis of the Effects on Muscle Strength and Size, Muscle Quality, and Functional Capacity.

Effective manipulation of the acute variables of resistance training is critical to optimizing muscle and functional adaptations in middle-aged and older adults. However, the ideal volume prescription (e.g., number of sets performed per exercise) in middle-aged and older adults remains inconclusive in the literature. The effects of single versus multiple sets per exercise on muscle strength and size, muscle quality, and functional capacity in middle-aged and older adults were compared. Moreover, the effects of single versus multiple sets per exercise on muscular and functional gains were also examined, considering the influence of training duration. Randomized controlled trials and non-randomized controlled trials comparing single versus multiple sets per exercise on muscle strength, muscle size, muscle quality, or functional capacity in middle-aged and older adults (aged ≥ 50years) in the PubMed/MEDLINE, Web of Science, and Scopus databases (01/09/2021, updated on 15/05/2022) were identified. A random-effects meta-analysis was used. Fifteen studies were included (430 participants; 93% women; age 57.9-70.1years). Multiple sets per exercise produced a greater effect than single sets on lower-limb strength (standardized mean difference [SMD] = 0.29; 95% confidence interval [CI] 0.07-0.51; mean difference [MD] = 1.91kg; 95% CI 0.50-3.33) and muscle quality (SMD = 0.40; 95% CI 0.05-0.75) gains. There were no differences between single versus multiple sets per exercise for upper-limb strength (SMD = 0.13; 95% CI - 0.14 to 0.40; MD = 0.11kg; 95% CI - 0.52 to 0.75), muscle size (SMD = 0.15; 95% CI - 0.07 to 0.37), and functional capacity (SMD = 0.01; 95% CI - 0.47 to 0.50) gains. In addition, there were no differences between single versus multiple sets on muscle strength and size gains for training durations ≤ 12weeks or > 12weeks. Multiple sets per exercise produced greater lower-limb strength and muscle quality gains than single sets in middle-aged and older adults, although the magnitude of the difference was small. In contrast, single sets per exercise were sufficient to improve upper-limb strength, muscle size, and functional capacity in these populations. Despite these findings, researchers should conduct future high-quality, pre-registered, and blinded randomized controlled trials to strengthen the scientific evidence on this topic.

Sarcomere dynamics revealed by a myofilament integrated FRET-based biosensor in live skeletal muscle fibers

The sarcomere is the functional unit of skeletal muscle, essential for proper contraction. Numerous acquired and inherited myopathies impact sarcomere function causing clinically significant disease. Mechanistic investigations of sarcomere activation have been challenging to undertake in the context of intact, live skeletal muscle fibers during real time physiological twitch contractions. Here, a skeletal muscle specific, intramolecular FRET-based biosensor was designed and engineered into fast skeletal muscle troponin C (TnC) to investigate the dynamics of sarcomere activation. In transgenic animals, the TnC biosensor incorporated into the skeletal muscle fiber sarcomeres by stoichiometric replacement of endogenous TnC and did not alter normal skeletal muscle contractile form or function. In intact single adult skeletal muscle fibers, real time twitch contractile data showed the TnC biosensor transient preceding the peak amplitude of contraction. Importantly, under physiological temperatures, inactivation of the TnC biosensor transient decayed significantly more slowly than the Ca2+ transient and contraction. The uncoupling of the TnC biosensor transient from the Ca2+ transient indicates the biosensor is not functioning as a Ca2+ transient reporter, but rather reports dynamic sarcomere activation/ inactivation that, in turn, is due to the ensemble effects of multiple activating ligands within the myofilaments. Together, these findings provide the foundation for implementing this new biosensor in future physiological studies investigating the mechanism of activation of the skeletal muscle sarcomere in health and disease.

Ablation of Calsequestrin-1, Ca2+ unbalance, and susceptibility to heat stroke.

Introduction: Ca2+ levels in adult skeletal muscle fibers are mainly controlled by excitation-contraction (EC) coupling, a mechanism that translates action potentials in release of Ca2+ from the sarcoplasmic reticulum (SR) release channels, i.e. the ryanodine receptors type-1 (RyR1). Calsequestrin (Casq) is a protein that binds large amounts of Ca2+ in the lumen of the SR terminal cisternae, near sites of Ca2+ release. There is general agreement that Casq is not only important for the SR ability to store Ca2+, but also for modulating the opening probability of the RyR Ca2+ release channels. The initial studies: About 20 years ago we generated a mouse model lacking Casq1 (Casq1-null mice), the isoform predominantly expressed in adult fast twitch skeletal muscle. While the knockout was not lethal as expected, lack of Casq1 caused a striking remodeling of membranes of SR and of transverse tubules (TTs), and mitochondrial damage. Functionally, CASQ1-knockout resulted in reduced SR Ca2+ content, smaller Ca2+ transients, and severe SR depletion during repetitive stimulation. The myopathic phenotype of Casq1-null mice: After the initial studies, we discovered that Casq1-null mice were prone to sudden death when exposed to halogenated anaesthetics, heat and even strenuous exercise. These syndromes are similar to human malignant hyperthermia susceptibility (MHS) and environmental-exertional heat stroke (HS). We learned that mechanisms underlying these syndromes involved excessive SR Ca2+ leak and excessive production of oxidative species: indeed, mortality and mitochondrial damage were significantly prevented by administration of antioxidants and reduction of oxidative stress. Though, how Casq1-null mice could survive without the most important SR Ca2+ binding protein was a puzzling issue that was not solved. Unravelling the mystery: The mystery was finally solved in 2020, when we discovered that in Casq1-null mice the SR undergoes adaptations that result in constitutively active store-operated Ca2+ entry (SOCE). SOCE is a mechanism that allows skeletal fibers to use external Ca2+ when SR stores are depleted. The post-natal compensatory mechanism that allows Casq1-null mice to survive involves the assembly of new SR-TT junctions (named Ca2+ entry units) containing Stim1 and Orai1, the two proteins that mediate SOCE.

Trichinella spiralis-derived extracellular vesicles induce a protective immunity against larval challenge in mice.

Human trichinellosis is a serious disease with no effective treatment till now. Recently, the protective immunity induced by parasite-derived extracellular vesicles (EVs) are studied for some parasites such as Echinostoma caproni. The current study aimed to investigate the novel Trichinella spiralis-derived EVs as a potential vaccine candidate for the first time in a mouse model. Trichinella spiralis EVs were isolated and identified using transmission electron microscopy, gel electrophoresis, protein content measurements, and beads-based flow cytometry. Vaccination was done by subcutaneous injection of two doses of 3.5μg T. spiralis-derived EVs. We observed a significant reduction in T. spiralis adult worm and muscle larval counts in mice immunized with T. spiralis-derived EVs (EVs-Ts group) and controlled inflammatory changes in the intestine and muscles. The EVs-Ts group showed a higher level of IFN- γ, whereas the IL-4 secretion was elevated more in the EVs group (EVs group) and showed a lower level after challenge with T. spiralis infection (EVs-Ts group). This implies a mixed Th1/Th2 immune response with obvious Th1 polarization. Moreover, elevation of serum T. spiralis-specific IgG was reported. In conclusion, this preliminary study provides T. spiralis EVs as a promising candidate for future development of anti-Trichinella vaccine.

Multidisciplinary and Nonpharmacological Management of Pain in Temporomandibular Disorders (TMDs).

Temporomandibular joint dysfunction (TMD) is not a single diagnosis, but a term covering a group of conditions that involve pain and dysfunction of the masticatory muscles within the temporomandibular joint (TMJ) and associated structures. It is a set of disease entities comprising various ailments and clinical symptoms. One of the most distressing symptoms for TMD patients is pain. Pain is subjective and always unpleasant. The VAS (visual analogue scale) was used in this research. The aim of this study was to assess the influence of physical stimuli, namely extremely low frequency magnetic field (ELF-MF) and LED light, on the experience of pain caused by increased tension in the masticatory muscles in adults. Out of 150 people examined, 104 were enrolled in the study after meeting the eligibility criteria. The study group was divided into 4 subgroups. Each subgroup received physical therapy treatment using a different physical stimulus. The effects of four therapeutic modalities were compared. In terms of VAS scores, pain attenuation was observed in all subgroups. The study confirmed the analgesic effect of the selected physical therapy methods. The authors focused on the analysis of the results obtained for each subgroup, comparing the effects of individual modalities on pain intensity (according to VAS scores). After the treatment, pain relief was observed in each of the studied subgroups. Treatment using ELF-MF and ELF-MF in combination with LED light in the course of TMD brings about a significant improvement in the subjective pain experience expressed in VAS pain scores. The use of selected physical stimuli and their beneficial effect on pain symptoms during mandibular movements has important implications for patients' daily life and work. Incorporation of therapeutic methods can help enhance patient satisfaction and comfort during manual TMJ therapy and lengthy dental procedures.

MSTN Regulatory Network in Mongolian Horse Muscle Satellite Cells Revealed with miRNA Interference Technologies.

Myostatin (MSTN), a member of the transforming growth factor-β superfamily, inhibits the activation of muscle satellite cells. However, the role and regulatory network of MSTN in equine muscle cells are not well understood yet. We discovered that MSTN knockdown significantly reduces the proliferation rate of equine muscle satellite cells. In addition, after the RNA sequencing of equine satellite cells transfected with MSTN-interference plasmid and control plasmid, an analysis of the differentially expressed genes was carried out. It was revealed that MSTN regulatory networks mainly involve genes related to muscle function and cell-cycle regulation, and signaling pathways, such as Notch, MAPK, and WNT. Subsequent real-time PCR in equine satellite cells and immunohistochemistry on newborn and adult muscle also verified the MSTN regulatory network found in RNA sequencing analysis. The results of this study provide new insight into the regulatory mechanism of equine MSTN.

Motor unit involvement in scalene, strenocleidomastoid, and rectus abdominis muscles during eupnea, tachypnea, and bradypnea of sedentary young male adults: an observational study

Background: It is well-established that extra-diaphragmatic muscles participate in respiration depending on the physiological situation. Even in clinical conditions where the diaphragm cannot act optimally, extra-diaphragmatic muscles can compensate for the breathing mechanics. Aim of the study: This study aims to determine the role of motor units in various respiratory conditions by monitoring the motor unit discharge in the scalene, sternocleidomastoid, and rectus abdominis during eupnea, tachypnea, and bradypnea using surface electromyography (sEMG). Material and methods: In this study, 28 healthy, sedentary males without a history of ailments participated. Using sEMG, the motor unit discharges from the scalene, sternocleidomastoid, and rectus abdominis were measured in three breathing patterns: normal breathing, hyperventilation, and intermittent breath retention. Results: The motor unit discharges of the rectus abdominis during eupnea, bradypnea, and tachypnea were significantly different, indicating that only the rectus abdominis' motor units were actively involved. Rectus abdominis muscle experienced changes in motor unit discharges that were highest and lowest during tachypnea and bradypnea, respectively [p&lt;0.05]. Conclusions: This study has tried to evaluate the role of the motor units of three extra-diaphragmatic muscles in healthy sedentary young male adults with different respiratory conditions. This study has revealed that the rectus abdominis actively participates in the physiological conditions in young, sedentary healthy adult males. In scalene and sternocleidomastoid, active involvement of the motor unit has not been observed.

Fetal muscle extract improves muscle function and performance in aged mice.

Background: Loss of skeletal muscle mass and function is one of the major musculoskeletal health problems in the aging population. Recent studies have demonstrated differential proteomic profiles at different fetal stages, which might be associated with muscle growth and development. We hypothesized that extract derived from fetal muscle tissues at the stage of hypertrophy could ameliorate the loss of muscle mass and strength in aged mice. Methods: To allow sufficient raw materials for investigation, skeletal muscle extract from fetal sheep at week 16 of gestation and maternal tissue were used in the present study. iTRAQ (isobaric tags for relative and absolute quantitation) and KEGG pathway analyses identified differentially expressed proteins in fetal sheep muscle extract vs. adult sheep muscle extract. Effects of FSME and ASME on human myoblast proliferation were studied. To examine the effect of FSME in vivo, C57BL/6 male mice at 20 months of age were subjected to intramuscular administration of FSME or vehicle control for 8 weeks. A grip strength test and ex vivo muscle force frequency test were conducted. Finally, serum samples were collected for multiplex analysis to determine potential changes in immunological cytokines upon FSME injection. Results: Compared with ASME, 697 and 412 peptides were upregulated and downregulated, respectively, in FSME, as indicated by iTRAQ analysis. These peptides were highly related to muscle development, function, and differentiation from GO enrichment analysis. FSME promoted cell proliferation of myoblast cells (+300%, p < 0.01) without causing significant cytotoxicity at the tested concentration range compared with ASME. After 8 weeks of FSME treatment, the percentage of lean mass (+10%, p < 0.05), grip strength (+50%, p < 0.01), and ability in fatigue resistance were significantly higher than those of the control group. Isometric forces stimulated by different frequencies were higher in the control group. Histologically, the control group showed a larger cross-sectional area (+20%, p < 0.01) than the FSME group. The multiplex assay indicated that FSME treatment did not lead to an elevated circulatory level of inflammatory cytokines. Of note, after FSME treatment, we observed a significant drop in the circulating level of IL-12 (p40) from 90.8 ± 48.3 pg/ml to 82.65 ± 4.4 pg/ml, G-CSF from 23476 ± 8341.9 pg/ml to 28.35 ± 24.2 pg/ml, KC from 97.09 ± 21.2 pg/ml to 29.2 ± 7.2 pg/ml, and RANTES from 325.4 ± 17.3 pg/ml to 49.96 ± 32.1 pg/ml. Conclusion: This is the first study demonstrating the beneficial effect of fetal muscle extract on muscle health in aged mice. Further analysis of the active ingredients of the extract will shed light on the development of a novel treatment for sarcopenia.

Impact of self-stretching techniques on piriformis muscles tightness in supine vs sitting position

Background and Purpose: Piriformis muscle is the deep gluteus muscle present at the posterior side of the hip joint. Its main function is external rotation of hip joint. Tightness of piriformis muscle is common these days due to sedentary life style. Due to tightness of piriformis muscle, the mobility of external rotation in hip joint also gets altered. The aim of this research is to compare the effect of self-stretching in supine vs sitting position on piriformis muscle in random young adults. Methodology: A sample size of 40 (n=40) random young adults were taken and divided into two groups (n1=20) (n2=20) of 20 each. The first group was asked to do self-stretching in supine position and second group was asked to do self-stretching in sitting position for 30 sec/stretch 10 times/session 2 times in a day. This intervention was given for a week. The outcome measures include piriformis muscle tightness test and goniometer measurement. Result: The result showed significant improvement in tightened piriformis muscle in self-stretching in supine and sitting group. Conclusion: The self-stretching in sitting group showed more improvement on piriformis muscle tightness than self-stretching in supine position.

FP.44 Exploring the role of MuscleBlind-Like proteins in the regulation of CaVB1 isoform expression in adult skeletal muscle

FP.44 Exploring the role of MuscleBlind-Like proteins in the regulation of CaVB1 isoform expression in adult skeletal muscle

P.149 Differential expression of intermediate filament proteins: lamins A/C and desmin within and between adult skeletal muscles

The cell cytoskeleton is composed of three main components: microfilaments, microtubules, and intermediate filaments. Intermediate filaments consist of intermediate filament proteins that are widely distributed in cells and tissues, either in the cytoplasm or the nucleus. Desmin is a tissue-specific cytoplasmic intermediate filament protein, while A-type lamins including lamin A/C are ubiquitously expressed nuclear intermediate filament proteins. Both play major roles in skeletal muscle functions. Mutations in the <i>DES</i> gene, encoding Desmin, and <i>LMNA</i> gene, encoding A-type lamins, lead to a group of rare disorders called desminopathies and laminopathies, respectively. The most frequent pathologies are those involving skeletal muscles. Despite the universal expression of lamins A/C in almost all cells and tissues, different phenotypes associated with laminopathies reflect a high degree of tissue-specificity, the reasons for which are not completely understood. It has also been shown that specific muscles/muscle groups are affected earlier than others in these myopathies. We hypothesized that desmin and lamins A/C are not uniformly expressed in different skeletal muscles and or muscle parts. Accordingly, we have investigated the relative expression of desmin, lamin A & lamin C in 9 skeletal muscles, of which 7 were divided into belly and myotendinous junction (MTJ). Our preliminary results revealed that there is no significant difference in the relative expression of desmin and lamins A/C between bellies and MTJs within a single muscle. We also observed that the relative expression of lamins A & C is correlated with myogenic markers; MyoD and myogenin, while desmin is not. Strikingly, FDB muscle showed the highest expression of lamins A/C compared to other muscles. We are currently investigating desmin, lamin A and lamin C protein levels by western blot and immunohistochemistry and the effect of age and exercise on the expression of these intermediate filament proteins.

ATIVAÇÃO DE CÉLULAS SATÉLITES E RESPOSTA NA VIA DE SINALIZAÇÃO NOS EXERCÍCIOS ARTICULARES DOS ATLETAS

ABSTRACT Introduction: Skeletal muscle satellite cells are considered the unique source of stem cells for myogenic differentiation of adult skeletal muscle cells. Upon stimulation, the skeletal muscle satellite cell can be activated through specific signaling pathways, proliferate and differentiate into a muscle cell. An analysis of the effects of key signaling pathways could provide the basis for an in-depth study of skeletal muscle formation in athletes and muscle development. Objective: This paper analyzes the effects of key signaling pathways on skeletal muscle satellite cell proliferation and differentiation. Methods: We divided 32 athletes into four groups: control, stretching, experimental, and mixed groups. The control group received no training at all, the stretching group and the experimental group received stretching training on the right gastrocnemius. The mixed group also got weight climbing training in the stretching training, initial load 30% of the athlete's weight, increasing 25% each week until 100% of body weight, at the frequency of 3 times a week. After training, gene expression of live satellite cells was measured by intramuscular signaling. Results: The FGM level of the antagonistic group (3.56±0.21) was higher than in the control group (3.25±0.18). The gene expression of HGF mRNA was higher in the mixed group (2.16±0.24) followed by the antagonistic group (2.02±0.15), the stretching group (1.81±0.25), and the control group (1.03±0.06). Conclusion: Both stretching and antagonistic training can increase gene expression in signaling pathways. Antagonistic training significantly increased the expression of HGF, MGF, and mRNA. This activity can promote muscle bulking and skeletal muscle enlargements. Evidence Level II; Therapeutic Studies - Investigating the result.

Effect of caffeine on mitochondrial biogenesis in the skeletal muscle - A narrative review.

Caffeine is one of the most widely used substances as recreational drug for performance-enhancement in sport, underpinned by a strong evidence base. Although the effects of caffeine are widely investigated within the scope of performance physiology, the molecular effects of caffeine within skeletal muscle remain unclear. Evidence from invitro and invivo models suggest that caffeine regulates the glucose metabolism in the skeletal muscle. Moreover, caffeine seems to stimulate CaMKII, PPARδ/β, AMPK and PGC1α, classical markers of exercise-adaptations, including mitochondrial biogenesis and mitochondrial content. This review summarizes evidence to suggest caffeine-effects within skeletal muscle fibers, focusing on the putative role of caffeine on mitochondrial biogenesis to explore whether caffeine supplementation might be a strategy to enhance mitochondrial biogenesis.

Reliability of TMS measurements using conventional hand-hold method with different numbers of stimuli for tibialis anterior muscle in healthy adults.

Objective: The objective of this study was to determine the reliability of corticomotor excitability measurements using the conventional hand-hold transcranial magnetic stimulation (TMS) method for the tibialis anterior (TA) muscle in healthy adults and the number of stimuli required for reliable assessment.Methods: Forty healthy adults participated in three repeated sessions of corticomotor excitability assessment in terms of resting motor threshold (rMT), slope of recruitment curve (RC), peak motor evoked potential amplitude (pMEP), and MEP latency using conventional TMS method. The first two sessions were conducted with a rest interval of 1 h, and the last session was conducted 7–10 days afterward. With the exception of rMT, the other three outcomes measure elicited with the block of first 3–10 stimuli were analyzed respectively. The within-day (session 1 vs. 2) and between-day (session 1 vs. 3) reliability for all four outcome measures were assessed using intraclass correlation coefficient (ICC), standard error of measurement, and minimum detectable difference at 95% confidence interval.Results: Good to excellent within-day and between-day reliability was found for TMS-induced outcome measures examined using 10 stimuli (ICC ≥ 0.823), except in pMEP, which showed between-day reliability at moderate level (ICC = 0.730). The number of three stimuli was adequate to achieve minimum acceptable within-day reliability for all TMS-induced parameters and between-day reliability for MEP latency. With regard to between-day reliability of RC slope and pMEP, at least seven and nine stimuli were recommended respectively.Conclusion: Our findings indicated the high reliability of corticomotor excitability measurement by TMS with adequate number of stimuli for the TA muscle in healthy adults. This result should be interpreted with caveats for the specific methodological choices, equipment setting, and the characteristics of the sample in the current study.Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100045141.