Skeletal Muscle Disease Research Articles

Visualizing sarcomere and cellular dynamics in skeletal muscle to improve cell therapies.

The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling. We find titin's integration into the sarcomere tightly regulated and its unexpected mobility facilitating a homogeneous distribution of titin after cell fusion - an integral part of syncytium formation and maturation of skeletal muscle. In adult mCherry-titin mice, treatment of muscle injury by implantation of titin-eGFP myoblasts reveals how myocytes integrate, fuse, and contribute to the continuous myofilament system across cell boundaries. Unlike in immature primary cells, titin proteins are retained at the proximal nucleus and do not diffuse across the whole syncytium with implications for future cell-based therapies of skeletal muscle disease.

Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review.

AKG, a central metabolite in the Krebs cycle, plays a vital role in cellular energy production and nitrogen metabolism. This review explores AKG's potential therapeutic applications in skeletal muscle health and exercise performance, focusing on its mechanisms for promoting muscle regeneration and counteracting muscle atrophy. A literature search was conducted using the PubMed, Web of Science, and Scopus databases, yielding 945 articles published up to 31 October 2024. Of these, 112 peer-reviewed articles met the inclusion criteria and formed the basis of this review. AKG supports muscle recovery by stimulating muscle satellite cells (MuSCs) and macrophage polarization, aiding muscle repair and reducing fibrosis. Additionally, AKG shows promise in preventing muscle atrophy by enhancing protein synthesis, inhibiting degradation pathways, and modulating inflammatory responses, making it relevant in conditions like sarcopenia, cachexia, and injury recovery. For athletes and active individuals, AKG supplementation has enhanced endurance, reduced fatigue, and supported faster post-exercise recovery. Despite promising preliminary findings, research gaps remain in understanding AKG's long-term effects, optimal dosage, and specific pathways, particularly across diverse populations. Further research, including large-scale clinical trials, is essential to clarify AKG's role in muscle health and to optimize its application as a therapeutic agent for skeletal muscle diseases and an enhancer of physical performance. This review aims to provide a comprehensive overview of AKG's benefits and identify future directions for research in both clinical and sports settings.

Ion‐Permeable Electrospun Scaffolds Enable Controlled In‐Vitro Electrostimulation Assay of Myoblasts

AbstractIn‐vitro models are fundamental for studying muscular cell contractility and for wide‐screening of therapeutic candidates targeting skeletal muscle diseases, owing to their scalability, reproducibility, and circumvention of ethical concerns. However, in‐vitro assays permitting reliable electrical stimulation of cell contractile activity still require technological development. Here, a novel approach to electrically stimulate differentiated muscular cell contractility is reported exploiting the ionic conductivity and mechanical flexibility of 3D nanofibrous scaffolds. The electrospun poly(L‐lactide‐co‐caprolactone) scaffold allowed for C2C12 murine myoblasts horizontal elongation and myotubes formation. Scaffold porosity enables high ionic conductivity and strong electric field generation, orthogonally oriented to the scaffold surface. Electrically induced cell contractility is determined with atomic force microscopy (AFM) enabling real‐time monitoring of scaffold vibrations in liquid environment. Differentiated cell actuation is found to be linearly correlated to current amplitude and number of current stimuli. Integrating the 3D nanofibrous scaffolds with real‐time AFM monitoring provides highly accurate in‐vitro assays for biomedical research. The induction of electric fields orthogonal to the scaffold surface allows for accurately mimicking the excitation‐contraction coupling mechanism observed in native skeletal muscle tissue. This work paves the way for the quantitative study of muscular cell dynamic behavior and physiology, further evaluating therapy effectiveness for muscular pathologies.

Asymmetric Cell Division and Satellite Cell Fate Regulation in Skeletal Muscle Aging and Disease

Asymmetric Cell Division and Satellite Cell Fate Regulation in Skeletal Muscle Aging and Disease

Role of four and a half LIM domain protein 1 in tumors (Review).

As a cytoskeletal protein, the four and a half LIM domain protein 1 (FHL1) is widely expressed in various cells, particularly skeletal and cardiac muscle cells. FHL1 is involved in the development of the skeletal muscle and myocardium, regulations of gene transcription and thyroid function, and other physiological processes. Its expression is closely related to numerous diseases, such as skeletal muscle disease and viral infections. With the advances in research, the role of FHL1 in the development of tumors is also being revealed. The mechanism of FHL1 in the regulation of tumor growth is complex and is becoming a research focus. It is also expected to become a potential target for tumor therapy. Therefore, the present article reviewed the progress in research on the role of FHL1 in cancer.

Evaluation of Sarcopenia by Psoas Muscle Measurements in Bullous Pemphigoid: A Single-Institution Survey in Japan.

Bullous pemphigoid (BP) is a rare autoimmune blistering disease that primarily affects elderly individuals. Based on the Bullous Pemphigoid Disease Area Index (BPDAI) severity assessment, immunosuppressive drugs are recommended for severe cases that fall within the more than moderate classes. Sarcopenia, which is characterized by decreased skeletal muscle mass and function in elderly patients, is a progressive and widespread skeletal muscle disease. We retrospectively surveyed patients who received treatment for BP at our hospital between 2012 and 2024 to evaluate the relevance of sarcopenia, as assessed using the psoas muscle mass index (PMI), and to investigate the benefit of relapse-free survival (RFS). A total of 59 patients with BP were included in this study. A total of 57.6% (34 of 59 patients) of the BP patients had sarcopenia, as measured by PMI. Kaplan-Meier analysis showed that the sarcopenia group (n = 34) had a median RFS of 394 days, which was not longer than that of the non-sarcopenia group (n = 25, 275 days) (p = 0.894). No significant difference in RFS was observed in the subgroup analysis based on the severity of BPDAI. Our real-world data confirmed the high prevalence of sarcopenia in the BP population and the efficacy of standard treatment centered on immunosuppressive therapy based on the severity of BPDAI. There is little basis for reducing oral corticosteroids below 0.5 mg/kg based solely on the patient's perceived frailty, regardless of the severity of the BPDAI. Limited evidence is available to assess the association between sarcopenia and autoimmune diseases in terms of their etiology. As populations continue to age globally, it is important for clinicians to prioritize addressing diseases while considering whether patients experience frailty in daily practice.

Prevalence of sarcopenia in heart failure with mildly reduced ejection fraction and its impact on clinical outcomes

Background Sarcopenia is a progressive age-related skeletal muscle disease associated with adverse outcomes in those with cardiovascular disease. In this study, the prevalence of sarcopenia and its effect on clinical outcomes in heart failure with mildly reduced ejection fraction (HFmrEF) patients were examined. Methods A total of 722 patients from three centres who applied to the outpatient clinic with the diagnosis of HFmrEF between 01 January 2020 and 01 June 2021 were included in the study retrospectively. Sarcopenia was diagnosed with a screening test using age, grip srength and calf circumference. At least two-year follow-up results were reviewed from the date the patients were included in the study. Results Of the 722 HFmrEF patients, 169 (23.4%) were sarcopenic. During the follow-up of sarcopenic patients, a higher rate of hospitalisation and two-year mortality was detected compared to the non-sarcopenic group (49.7% vs 33.3%, p < .001 and 23.7% vs 13.2%, p = .001, respectively). Additionally, atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), chronic renal failure (CRF) and smoking were detected at higher rates in sarcopenic patients. In subgroup analysis, AF was found to be significantly higher in overweight/obese sarcopenia patients compared to other groups. According to Receiver operating characteristic (ROC) analysis, the sarcopenia score cut-off of 73.61 predicted mortality with 65% sensitivity and 63% specificity, and the cut-off level of 71.10 predicted hospitalisation with 68% sensitivity and 69% specificity. Conclusion In HFmrEF patients, sarcopenia is associated with adverse events and is an important prognostic marker.

Electrical stimulation of biofidelic engineered muscle enhances myotube size, force, fatigue resistance, and induces a fast-to-slow-phenotype shift.

Therapeutic development for skeletal muscle diseases is challenged by a lack of exvivo models that recapitulate human muscle physiology. Here, we engineered 3D human skeletal muscle tissue in the Biowire II platform that could be maintained and electrically stimulated long-term. Increasing differentiation time enhanced myotube formation, modulated myogenic gene expression, and increased twitch and tetanic forces. When we mimicked exercise training by applying chronic electrical stimulation, the "exercised" skeletal muscle tissues showed increased myotube size and a contractility profile, fatigue resistance, and gene expression changes comparable to invivo models of exercise training. Additionally, tissues also responded with expected physiological changes to known pharmacological treatment. To our knowledge, this is the first evidence of a human engineered 3D skeletal muscle tissue that recapitulates invivo models of exercise. By recapitulating key features of human skeletal muscle, we demonstrated that the Biowire II platform may be used by the pharmaceutical industry as a model for identifying and optimizing therapeutic drug candidates that modulate skeletal muscle function.

Promoting and accelerating muscle regeneration through cell therapy in a mouse model

ObjectivesSkeletal muscle injuries and disorders are universal clinical challenges with direct and indirect mechanisms and notable residual effects, such as prolonged, intense pain and physical disability. Stem cells, an innovative tool for cell therapy for musculoskeletal disorders, specifically promote skeletal muscle regeneration. This study was aimed at investigating the use of mesenchymal stem cells (MSCs) and their differentiated myocytes as a cell-based therapy to promote regeneration in damaged or diseased skeletal muscle. MethodsBone marrow mesenchymal stem cells (BM-MSCs) were isolated from the bone marrow of adult mice and grown in tissue culture flasks. The BM-MSCs were positive for CD90 and CD105, and negative for CD45 and CD34. These cells were induced with specific differentiation medium in vitro to differentiate into a skeletal muscle cell lineage over 7 days. Skeletal muscle differentiation was characterized according to morphology through hematoxylin and eosin staining, and scanning electron microscopy. Immunostaining for Myf-6, myosin heavy chain (MHC), and desmin—specific factors for skeletal muscle development—was performed to confirm skeletal muscle differentiation. An in vivo study in a muscle injury model was used to evaluate cell therapy based on naïve stem cells and differentiated myocytes. ResultsCultured mouse BM-MSCS were positive for CD90 and CD105, and negative for CD45 and CD34. These cells developed into skeletal muscle with strong skeletal muscle differentiation potential, as confirmed by immunohistochemistry for the markers Myf6, MHC, and desmin. The differentiated myocytes showed better repair enhancement than undifferentiated stem cells after transplantations into a mouse model of skeletal muscle atrophy. ConclusionsMyocytes derived from BM-MSCs may be incorporated into muscular atrophy treatment as a biological strategy for managing skeletal muscle diseases and injuries, thus advancing cell-based clinical treatments.

666P MyoScreen™ infantile and late-onset Pompe human skeletal muscle disease models for drug discovery and development of next-generation gene therapies

666P MyoScreen™ infantile and late-onset Pompe human skeletal muscle disease models for drug discovery and development of next-generation gene therapies

Knockout of rbm24a and rbm24b genes in zebrafish impairs skeletal and cardiac muscle integrity and function during development.

Skeletal and cardiac muscles are contractile tissues whose development and function are dependent on genetic programs that must be precisely orchestrated in time and space. In addition to transcription factors, RNA-binding proteins tightly regulate gene expression by controlling the fate of RNA transcripts, thus specific proteins levels within the cell. Rbm24 has been identified as a key player of myogenesis and cardiomyogenesis in several vertebrates, by controlling various aspects of post-transcriptional regulation, including pre-mRNA alternative splicing and mRNA stabilization. In zebrafish, knockdown of rbm24a or rbm24b also causes skeletal and cardiac muscle phenotypes, but how their combined loss affects muscle integrity and function remains elusive. By genome editing, we have generated rbm24a and rbm24b single mutants as well as double mutants. Structural analyses indicate that homozygous rbm24a and rbm24b double mutants exhibit severe somitic muscle and cardiac phenotypes, although rbm24b single mutants are obviously normal. We further show that the loss of rbm24a and rbm24b disrupts sarcomere organization, impairing functional contractility and motility of skeletal and cardiac muscles. The rbm24 mutant zebrafish represents a new genetic tool for in-depth studies of Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, disease and regeneration.

Pathomechanisms of Monoallelic variants in TTN causing skeletal muscle disease.

Pathogenic variants in the titin gene (TTN) are known to cause a wide range of cardiac and musculoskeletal disorders, with skeletal myopathy mostly attributed to biallelic variants. We identified monoallelic truncating variants (TTNtv), splice site or internal deletions in TTN in probands with mild, progressive axial and proximal weakness, with dilated cardiomyopathy frequently developing with age. These variants segregated in an autosomal dominant pattern in 7 out of 8 studied families. We investigated the impact of these variants on mRNA, protein levels, and skeletal muscle structure and function. Results reveal that nonsense-mediated decay likely prevents accumulation of harmful truncated protein in skeletal muscle in patients with TTNtvs. Splice variants and an out-of-frame deletion induce aberrant exon skipping, while an in-frame deletion produces shortened titin with intact N- and C-termini, resulting in disrupted sarcomeric structure. All variant types were associated with genome-wide changes in splicing patterns, which represent a hallmark of disease progression. Lastly, RNA-seq studies revealed that GDF11, a member of the TGF-β superfamily, is upregulated in diseased tissue, indicating that it might be a useful therapeutic target in skeletal muscle titinopathies.

SRSF2 is a key player in orchestrating the directional migration and differentiation of MyoD progenitors during skeletal muscle development

SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.

SRSF2 is a key player in orchestrating the directional migration and differentiation of MyoD progenitors during skeletal muscle development.

SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.

Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle.

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 4week 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. 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 4weeks, remodelled the skeletal muscle fibre proteome without any noticeable effects on energetic proteins. Short-term Mavacamten treatment may not be sufficient to reverse the muscle phenotype in nemaline myopathy.

Diarylpropionitrile-stimulated ERβ nuclear accumulation promotes MyoD-induced muscle regeneration in mdx mice by interacting with FOXO3A

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive degenerative disease of skeletal muscle, characterized by intramuscular inflammation, muscle regeneration disorder and replacement of muscle with fibroadipose tissue. DMD is caused by the absence of normal dystrophy. Impaired self-renew ability and limited differentiation capacity of satellite cells are proved as main reasons for muscle regeneration failure. The deficiency of estrogen impedes the process of muscle regeneration. However, the role of estrogen receptor β (ERβ) in muscle regeneration is still unclear. This study aims to investigate the role and the pharmacological effect of ERβ activation on muscle regeneration in mdx mice. This study showed that mRNA levels of ERβ and myogenic-related genes both witnessed increasing trends in dystrophic context. Our results revealed that treatment with selective ERβ agonist (DPN, diarylpropionitrile) significantly increased myogenic differentiation 1 (MyoD-1) level and promoted muscle regeneration in mdx mice. Similarly, in mdx mice with muscle-specific estrogen receptor α (ERα) ablation, DPN treatment still promoted muscle regeneration. Moreover, we demonstrated that myoblasts differentiation was accompanied by raised nuclear accumulation of ERβ. DPN treatment augmented the nuclear accumulation of ERβ and, thus, contributed to myotubes formation. One important finding was that forkhead box O3A (FOXO3A), as a pivotal transcription factor in Myod-1 transcription, participated in the ERβ-promoted muscle regeneration. Overall, we offered an interesting explanation about the crucial role of ERβ during myogenesis.

Discovery of selective Orai channel blockers bearing an indazole or a pyrazole scaffold

The calcium release activated calcium (CRAC) channel is highly expressed in T lymphocytes and plays a critical role in regulating T cell proliferation and functions including activation of the transcription factor nuclear factor of activated T cells (NFAT), cytokine production and cytotoxicity. The CRAC channel consists of the Orai pore subunit and STIM (stromal interacting molecule) endoplasmic reticulum calcium sensor. Loss of CRAC channel mediated calcium signaling has been identified as an underlying cause of severe combined immunodeficiency (SCID), leading to drastically weakened immunity against infections. Gain-of-function mutations in Orai and STIM have been associated with tubular aggregated myopathy (TAM), a skeletal muscle disease. While a number of small molecules have shown activity in inhibiting the CRAC signaling pathway, the usefulness of those tool compounds is limited by their off-target activity against TRPM4 and TRPM7 ion channels, high lipophilicity, and a lack of understanding of their mechanism of action. We report structure-activity relationship (SAR) studies that resulted in the characterization of compound 4k [1-(cyclopropylmethyl)-N-(3-fluoropyridin-4-yl)-1H-indazole-3-carboxamie] as a fast onset, reversible, and selective CRAC channel blocker. 4k fully blocked the CRAC current (IC50: 4.9 μM) and the nuclear translocation of NFAT at 30 and 10 μM, respectively, without affecting the electrophysiological function of TRPM4 and TRPM7 channels. Computational modeling appears to support its direction binding to Orai proteins that form the transmembrane CRACchannel.

The emerging roles of necroptosis in skeletal muscle health and disease.

Necroptosis is a regulated form of cell death with implications in various physiological and pathological processes in multiple tissues. However, the relevant findings from post-mitotic tissues, such as skeletal muscle, are scarce. This review summarizes the potential contributions of necroptosis to skeletal muscle health and diseases. It first discusses the physiological roles of necroptosis in muscle regeneration and development. It then summarizes the contributions of necroptosis to the pathogenesis of multiple muscle diseases, including muscular dystrophies, inflammatory myopathies, cachexia, and neuromuscular disorders. Lastly, it unravels the gaps in our understanding and therapeutic challenges of inhibiting necroptosis as a potential intervention for muscle diseases. Specifically, the findings from the transgenic animal models and the use of pharmacological inhibitors of necroptosis are discussed with relevance to improving the structure and/or function of skeletal muscle in various diseases. Recent developments from experimental animal models and clinical data are presented to discuss the roles of necroptosis in skeletal muscle health and diseases.

Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.

Exercise training is considered a nonpharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete 4 wk of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial, and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimens need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.NEW & NOTEWORTHY This is the first study to investigate the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TDP-43 pathology and motor dysfunction, to perform exercise training. We demonstrate that despite the ALS-reminiscent aggressive disease progression characterizing the rNLS8 mouse model, rNLS8 mice are capable of performing mild-to-moderate endurance treadmill training for at least 3-4 wk. We demonstrate that exercise training induces several minor skeletal muscle adaptations without delaying disease progression in rNLS8 mice.

Method of Diagnosing Sarcopenia in Morbidly Obese Patients

Introduction. Sarcopenia refers to a clinical syndrome characterized by progressive skeletal muscle disease, loss of muscle mass and strength resulting in impaired physical performance. The prevalence of sarcopenia in the population ranges from 5% to 13% in people aged 43.0 ± 11.1 years and reaches 50% in those over 70. Various methods have been used to diagnose sarcopenia, which, however, have their limitations. Currently, CT scanning is considered the most accurate method for the detection of sarcopenia. Therefore, the development of new methods for early diagnosis of sarcopenia appears relevant. Aim. To investigate different methods of diagnosing sarcopenia in morbidly obese patients. Materials and methods. The study presents an analysis of various methods for diagnostics of sarcopenia in morbidly obese patients, including a patented method based on the research conducted in the BSMU Clinic (Utility Patent No. 2815157 dated 11.03.2024). Results and discussion. Doctors used the suggested method of diagnosis, defined the value of sarcopenia index equal or less than 15, and diagnosed sarcopenia. Conclusion. The prevalence and severity of sarcopenia vary depending on the classification criteria and thresholds used. Since a unified diagnostic method is yet to be developed, it is necessary to continue research into this issue, and introduce sarcopenia detection, prevention, and correction techniques into widespread clinical practice. Indices of sarcopenia and obesity, obtained during an additional preoperative study, provide significant prognostic information superior to body mass index, thereby enabling the direction and scope of surgical interventions to be determined and survival outcomes to be improved.