Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Automated Classification of Neuromuscular Diseases Using Thigh Muscle MRI With Model Interpretations","authors":"Lotte Huysmans,&nbsp;Louise Iterbeke,&nbsp;Bram De Wel,&nbsp;Matthias Opsomer,&nbsp;Kristl G. Claeys,&nbsp;Frederik Maes","doi":"10.1002/jcsm.70102","DOIUrl":"10.1002/jcsm.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuromuscular diseases (NMDs) are diagnosed using a combination of clinical evaluation, electromyography, nerve conduction studies, blood tests, muscle biopsy, and genetic testing. In addition, muscle magnetic resonance imaging (MRI) is used to visualise affected areas and allows the identification of fatty replacement of muscle tissue, muscle atrophy and oedema. The distinct muscle involvement patterns can be used to help in the diagnosis of NMDs. Our aim was to develop an automatic approach with interpretations that explain the model's decision to classify NMDs based on symptomatic MRI scans of the upper leg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used 109 Dixon muscle MRI scans of the upper legs of four different NMDs: limb–girdle muscular dystrophy type R12 (LGMDR12), Becker muscular dystrophy (BMD), myotonic dystrophy type 1 (DM1), Charcot–Marie–Tooth neuropathy type 1A (CMT1A) and healthy controls (HC). A U-Net was trained to segment all 18 muscles in the upper leg from which the fat fractions are calculated and used as input to a random forest classification model. SHapley Additive exPlanations (SHAP) are used to get an understanding of the reasoning of the model and are compared with muscle involvement patterns previously described in the medical literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The baseline models demonstrate strong performance in distinguishing between different classes, as evidenced by an overall accuracy of 89% and high area under the receiver operating characteristic curve (AUC) values for every class: 0.972, 0.983, 0.960, 0.990 and 0.997 for respectively LGMDR12, BMD, DM1, CMT1A and HC. In addition, we demonstrated that no significant difference could be observed with models trained on features calculated from ground truth segmentations, features calculated from a limited field of view or Mercuri score features. SHAP explanations help understand the decision of the models and can be linked to muscle patterns described in the medical literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A fully automated method was developed that is effective in distinguishing between four NMDs and healthy controls.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic Damage in Ovarian Cancer–Associated Cachexia Is Driven by Activin A Signalling","authors":"Amirhossein Abazarikia,&nbsp;Wonmi So,&nbsp;Yi Luan,&nbsp;Chandramohan Kattamuri,&nbsp;Thomas B. Thompson,&nbsp;So-Youn Kim","doi":"10.1002/jcsm.70096","DOIUrl":"10.1002/jcsm.70096","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cancer-associated cachexia (CAC) is a severe metabolic disorder characterized by involuntary weight loss, skeletal muscle atrophy and adipose tissue depletion. It is a major contributor to morbidity and mortality in the advanced stages of various cancers. However, the impact of CAC on the pancreas remains largely unexplored.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used mice with constitutively active &lt;i&gt;PI3K&lt;/i&gt; in oocytes, generated through a Cre-inducible &lt;i&gt;Pik3ca*&lt;/i&gt; knock-in allele driven by &lt;i&gt;Gdf9&lt;/i&gt;-icre and performed histological and molecular analyses of the pancreas during cachexia development. Additionally, we examined pancreatic changes following ovariectomy and administration of Follistatin 288 (FST288).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mice that developed cachexia symptoms associated with granulosa cell tumour (GCT) growth exhibited significant pancreatic atrophy compared to controls (Cre+ vs. Cre− at PD83, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), including reduced size of individual acinar cells (102.99 ± 12.19 μm&lt;sup&gt;2&lt;/sup&gt; vs. 207.94 ± 24.85 μm&lt;sup&gt;2&lt;/sup&gt; at PD83, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and acinar units (346.41 ± 169.22 μm&lt;sup&gt;2&lt;/sup&gt; vs. 1193.59 ± 136.01 μm&lt;sup&gt;2&lt;/sup&gt; at PD83, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), despite comparable food intake between groups. Acinar cells exhibited a decrease in zymogen granules, reduced amylase expression and diminished amylase activity in both serum (0.29 ± 0.08 vs. 1.41 ± 0.40, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and tissue (0.37 ± 0.14 vs. 1.05 ± 0.29, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). In contrast, pancreatic islets remained intact, as evidenced by histological analysis and preserved insulin expression. The pancreas of PD83 Cre+ mice also developed fibrosis and acinar cell death, characterized by elevated expression of collagen IV and α-SMA, and TUNEL-positive signals in acinar cells, respectively. Ovariectomy preserved body weight (2.66 ± 1.30 g for Cre+/OVX vs. 1.60 ± 0.97 g for Cre−) compared to Cre+ mice (−3.66 g) and maintained pancreatic function, suggesting that tumour-derived factors from GCT contribute to the severity of cachexia. Acinar cells showed high expression of ACVR2B, leading to activation of downstream p-SMAD3 signalling. Accordingly, activin A directly induced acinar cell atrophy in both ex vivo cultured pancreas (79.27 ± 19.03 μm&lt;sup&gt;2&lt;/sup&gt; vs. 171.14 ± 27.01 μm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and 266-6 acinar cells, as evidenced by reduced acinar cell size and decreased amylase production. Injection of FST288, an activin A inhibitor, rescued pancreatic acinar atrophy (252.95 ± 11.59 μm&lt;sup&gt;2&lt;/sup&gt; in Cre+/FST288 vs. 97.25 ± 12.37 μm&lt;sup&gt;2&lt;/sup&gt; in Cre+, &lt;i&gt;p&lt;/i","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcopenia and Its Individual Traits Independently Predict Mortality in Patients on Dialysis: A Systematic Review and Meta-Analysis","authors":"Alice Sabatino,&nbsp;Alessandro Guerra,&nbsp;Kenia Mara Baiocchi de Carvalho,&nbsp;Lilian Cuppari,&nbsp;Juan Jesus Carrero,&nbsp;Peter Stenvinkel,&nbsp;Bengt Lindholm,&nbsp;Carla Maria Avesani","doi":"10.1002/jcsm.70089","DOIUrl":"10.1002/jcsm.70089","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Loss of muscle mass, muscle weakness and the combination of the two are commonly observed in patients on dialysis and may have a negative impact on their survival. In this systematic review and meta-analysis (MA), we evaluated the consistency and strength of the association between mortality risk and the presence of low muscle mass with adequate muscle strength, low muscle strength with adequate muscle mass and sarcopenia (low muscle mass and strength combined) in patients on dialysis. Ultimately, we aimed to grade which of these three conditions had the strongest association with increased mortality risk in this vulnerable group of patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We searched for studies published until 31 January 2024 that evaluated sarcopenia and its individual components in patients aged &gt; 18 years on dialysis (haemodialysis and peritoneal dialysis) and that had a mean follow-up for mortality for ≥ 12 months. Included studies had to enable the evaluation of sarcopenia traits to identify patients with low muscle mass and adequate muscle strength, low muscle strength with adequate muscle mass, and sarcopenia. A systematic search was conducted in MEDLINE (by PubMed), Embase, Web of Science, Lilacs and grey literature (i.e., Google Scholar and ProQuest). We estimated consistency in the association between sarcopenia traits and death using random effects MA and reporting hazard ratio (HR) with a 95% confidence interval (95% CI).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The electronic search retrieved 5712 records. After removing duplicated records and those that did not meet the eligibility criteria, 19 studies were included in the qualitative synthesis (4281 participants) and 17 studies (4024 participants) with extractable data for the MA. The MA showed low heterogeneity in the association between muscle parameters and sarcopenia with the risk of death: &lt;i&gt;low muscle mass with adequate muscle strength,&lt;/i&gt; HR: 1.49; 95% CI: 1.04 to 2.13; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0%; &lt;i&gt;low muscle strength with adequate muscle mass,&lt;/i&gt; HR: 1.82; 95% CI: 1.38 to 2.41; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0%; and &lt;i&gt;sarcopenia,&lt;/i&gt; HR: 2.02; 95% CI: 1.61 to 2.54; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 40%.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Although being statistically significant, the association between low muscle mass and mortality seems to be less strong than the association between low muscle strength and mortality in patients on dialysis. Those presenting with a combination of the two traits, that is, sarcope","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Muscle PGC-1α Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis","authors":"Takuya Karasawa,&nbsp;Ran Hee Choi,&nbsp;Cesar A. Meza,&nbsp;Shinya Watanabe,&nbsp;J. Alan Maschek,&nbsp;Linda S. Nikolova,&nbsp;James E. Cox,&nbsp;Katsuhiko Funai","doi":"10.1002/jcsm.70090","DOIUrl":"10.1002/jcsm.70090","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The coupling of oxygen consumption to ATP synthesis via oxidative phosphorylation (OXPHOS) is central for cellular energy homeostasis. Some studies suggest exercise training increases the efficiency of ATP synthesis, but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes in mitochondrial lipids might influence OXPHOS efficiency (ATP produced per O&lt;sub&gt;2&lt;/sub&gt; consumed, referred to as P/O). Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional co-activator that coordinately regulates exercise-induced adaptations, including mitochondria. We hypothesized that increased PGC-1α activity might remodel mitochondrial membrane lipids and promote energy efficiency.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mice with skeletal muscle-specific overexpression of PGC-1α (MCK-PGC-1α) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by Western blotting. High-resolution respirometry and fluorometry analyses were performed to characterize mitochondrial bioenergetics (ATP production, O&lt;sub&gt;2&lt;/sub&gt; consumption and P/O) for permeabilized fibres and isolated mitochondria. Respiratory supercomplexes were assessed by blue native PAGE.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK-PGC-1α mice revealed that PGC-1α increases the concentrations of cone-shaped lipids such as phosphatidylethanolamine (PE; +25%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), cardiolipin (CL; +184%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and lysophospholipids (+34%–94%, all &lt;i&gt;p&lt;/i&gt; &lt; 0.01), while decreasing the concentrations of phosphatidylcholine (PC; −4%, &lt;i&gt;p&lt;/i&gt; = 0.0020), phosphatidylinositol (PI; −17%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and phosphatidic acid (PA; −35%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). However, while PGC-1α overexpression increased the abundance of OXPHOS enzymes (two- to fourfold, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), the rate of O&lt;sub&gt;2&lt;/sub&gt; consumption (1.5-fold, &lt;i&gt;p&lt;/i&gt; = 0.0030), or the respiratory supercomplexes (~1.5-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), P/O values were unaffected by PGC-1α overexpression in permeabilized fibres or isolated mitochondria.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Collectively, overexpression of PGC-1α promotes the biosynthesis of mitochondrial PE and CL, ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARC-18 Improved Motor Performance Through Inhibiting ACLY-Mediated Smad2/3 Acetylation in a Model of Duchenne Muscular Dystrophy","authors":"Chongyang Chen,&nbsp;Bingge Zhang,&nbsp;Chao Yang,&nbsp;Jing Wang,&nbsp;Ye He,&nbsp;Haitao Yu,&nbsp;Jianjun Liu,&nbsp;Yongmei Xie,&nbsp;Xifei Yang,&nbsp;Gong-Ping Liu","doi":"10.1002/jcsm.70081","DOIUrl":"10.1002/jcsm.70081","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness, with inflammation and fibrosis contributing to its pathogenesis. Despite advancements in genetic disease-modifying treatment, there is currently no effective pharmacological treatment for DMD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;New compound ARC-18, a derivative of Arctigenin known for its anti-inflammatory activity, was designed and synthesized in our lab and administered prophylactically to 2-month-old mdx mice for 60 days. The motor performance was investigated by rotarod test, climbing-pole test, grip strength test, hanging endurance test, treadmill endurance test and gait analysis. Afterwards, molecular biological experiments, including proteomics, immunohistochemistry, immunofluorescence, western blots, gene transfection and immunoprecipitation, were employed to investigate the molecular mechanism of ARC-18 in the treatment of mdx.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ARC-18 significantly ameliorated the motor performance of DMD mice (rotating time +65.9%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; hanging time +59.7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; grip strength +32.1%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; climbing time −29.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; numbers of electric shocks −69.3%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) by up-regulating the expression of dystrophin-associated proteins (dystrophin, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; α-dystroglycan, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and down-regulating the expression of muscle satellite/stem cell proteins (Pax7, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; Myod, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; Myog, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; α-SMA, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; fibronectin, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; collagen I, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). ARC-18 prevented the progression of muscle fibrosis, reduced inflammatory factors transforming growth factor (TGF) β1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), IL-1β (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and TNF-α (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) levels, and promoted the structural integrity of gastrocnemius and triceps muscles. Proteomics analysis demonstrated that ARC-18 treatment reversed the protein expression pattern of DMD model mice, with ATP-citrate synthase (ACLY) enriched in the TCA cycle pathway, showing a significant correlation with DMD expression levels (&lt;i&gt;R&lt;/i&gt; = −0.72, &lt;i&gt;p&lt;/i&gt; = 0.00031). Further investigations revealed that ARC-18 directly bound with ACLY (EC&lt;sub&gt;50&lt;/sub&gt; = 120.2 nM) to promote its degradation by the proteasome system and suppressed the ACLY-mediated acetylation of Smad2/3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) to reduce its nuclear localization (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) to inhibit fibrosis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Co","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance Exercise Intervention Restores Functional Capacity and Improves Frailty Biomarkers in Centenarians","authors":"Diego Marcos-Perez,&nbsp;Adrián Hernandez-Vicente,&nbsp;Sara Cruces-Salguero,&nbsp;Jon Landa,&nbsp;Michelle Bonvini,&nbsp;German Vicente-Rodríguez,&nbsp;Esther Pueyo,&nbsp;Leocadio Rodriguez-Mañas,&nbsp;Pedro Abizanda,&nbsp;David Otaegui,&nbsp;Nuria Garatachea,&nbsp;Ander Matheu","doi":"10.1002/jcsm.70079","DOIUrl":"10.1002/jcsm.70079","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Centenarians comprise an age group characterized by exceptional longevity and low age-associated pathologies. However, they still experience physiological decline, and different studies have linked frailty to this population. Exercise interventions reverse frailty and improve functional capacity, but no studies have addressed the effect of an intervention in centenarians. In this study, we assessed the impact of a 12-week resistance exercise intervention in a group of centenarians and characterized their functional capacity as well as the expression of several molecular biomarkers associated with frailty.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 19 centenarians were enrolled, but 7 of them did not complete the study. The remaining 12 centenarians were randomly assigned to the control or intervention group, which was a 12-week resistance exercise intervention. Molecular biomarkers were measured by qRT-PCR and ELISA.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The intervention group improved their functional capacity measured by Short Physical Performance Battery (SPPB) (post 5.0 vs 2.3 in pre) and Physical Performance and Mobility Examination (PPME) (6.5 vs 3.8), as well as in frailty status studied by Fried Frailty Phenotype (3.0 vs 3.8) and Frailty Trait Scale 5 (FTS5) (post 30.7 vs 34.0 in pre) scales. ANCOVA revealed that the resistance training led to significant improvements in functional capacity scales SPPB (&lt;i&gt;p&lt;/i&gt; = 0.01) and PPME (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), as well as Fried Frailty Phenotype (&lt;i&gt;p&lt;/i&gt; = 0.001) and FTS5 (&lt;i&gt;p&lt;/i&gt; = 0.05). Biomarkers related to frailty &lt;i&gt;(EGR1&lt;/i&gt;, &lt;i&gt;miR194-5p, miR125b-5p&lt;/i&gt; and &lt;i&gt;miR454-3p)&lt;/i&gt; and inflammation (&lt;i&gt;IL-&lt;/i&gt;6 and &lt;i&gt;IL-1β)&lt;/i&gt; showed different expression patterns in centenarians (&lt;i&gt;n&lt;/i&gt; = 19) compared to both old (&lt;i&gt;n&lt;/i&gt; = 44, average of 79 years old) and young adults (&lt;i&gt;n&lt;/i&gt; = 34, average of 29 years old) groups. Notably, the intervention was associated with improvements in frailty and inflammation biomarkers expression. Finally, correlation analyses showed significant associations between all functional and frailty variables, with SPPB correlating with &lt;i&gt;miR454-3p (ρ = 0.73)&lt;/i&gt; and FTS5 correlating with &lt;i&gt;miR454-3p (ρ = −0.83), IL-6 (ρ = 0.60)&lt;/i&gt; and &lt;i&gt;miR125b-5p (ρ = −0.55)&lt;/i&gt;.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our results revealed that resistance exercise intervention enhances functional status and reduces frailty in centenarians, and this is associated with improvements in frailty and inflammation biom","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Relative Energy Deficiency in Sport (REDs) on Bone Health in Elite Athletes: A Retrospective Analysis","authors":"Felix N. von Brackel,&nbsp;Robert Munzinger,&nbsp;Mikolaj Bartosik,&nbsp;Alexander Simon,&nbsp;Florian Barvencik,&nbsp;Ralf Oheim,&nbsp;Michael Amling","doi":"10.1002/jcsm.70082","DOIUrl":"10.1002/jcsm.70082","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Relative energy deficiency in sport (REDs) is associated with impaired performance and compromised bone health in elite athletes. While reduced bone mineral density (BMD) and increased risk for bone stress injuries are well documented, the underlying metabolic mechanisms remain poorly understood. This study investigates the bone metabolism in athletes with REDs and its impact on BMD and bone microstructure.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We retrospectively analysed data from 82 elite athletes (30.5% females, age 23.4 ± 7.6 years) who presented to our outpatient clinic. The diagnosis of REDs was made according to the International Olympic Committee REDs Clinical Assessment Tool Version 2 (IOC REDs CAT2), and athletes were categorised into strength-based vs. endurance-based sports. Laboratory assessment of calcium and bone metabolism included bone turnover markers such as osteocalcin, procollagen type 1 N-terminal propeptide (P1NP) and urinary deoxypyridinoline (DPD). Areal BMD with corresponding &lt;i&gt;Z&lt;/i&gt;-score was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and hip. Volumetric BMD and bone microstructure were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;REDs was diagnosed in 24% of the athletes, and stress fractures were observed more frequently in athletes with REDs compared with those without REDs (70% vs. 25%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Athletes with REDs showed significantly lower haemoglobin and haematocrit levels (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Osteocalcin and P1NP were reduced in REDs compared with athletes of strength-based disciplines (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), while urinary DPD/creatinine and calcium excretion were elevated (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), indicating suppressed bone formation and increased bone resorption, respectively. Athletes with REDs exhibited significantly reduced &lt;i&gt;Z&lt;/i&gt;-scores at the lumbar spine and hip compared with strength and endurance athletes without REDs (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). HR-pQCT revealed significantly lower bone volume to tissue volume and trabecular BMD at the distal radius and tibia, with more pronounced effects at the load-bearing tibia (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Similarly, trabecular number and cortical thickness were reduced in REDs, while no differences were observed in trabecular thickness.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Athletes with REDs are characterised by a catabolic bone metabolism, marked by reduced bone formati","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy","authors":"Andrea Farini,&nbsp;Francesco Strati,&nbsp;Monica Molinaro,&nbsp;Debora Mostosi,&nbsp;Sabrina Saccone,&nbsp;Luana Tripodi,&nbsp;Jacopo Troisi,&nbsp;Annamaria Landolfi,&nbsp;Chiara Amoroso,&nbsp;Barbara Cassani,&nbsp;Aitor Blanco-Míguez,&nbsp;Emma Leonetti,&nbsp;Davide Bazzani,&nbsp;Mattia Bolzan,&nbsp;Francesco Fortunato,&nbsp;Flavio Caprioli,&nbsp;Federica Facciotti,&nbsp;Yvan Torrente","doi":"10.1002/jcsm.70054","DOIUrl":"10.1002/jcsm.70054","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Duchenne Muscular Dystrophy (DMD) features immune-muscle crosstalk, where muscle fibre degeneration enhances pro-inflammatory macrophage infiltration, worsening inflammation and impairing regeneration.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We investigated the impact of immunoproteasome (IP) inhibition on the gut-muscle axis in mdx mice, a well-established model of DMD. We employed microbiota perturbation models, including broad-spectrum antibiotic treatment (ABX) and faecal microbiota transplantation (FMT) from IP-inhibited mdx mice. IP inhibition effects were assessed by analysing gut microbiota composition, intestinal inflammation, muscle integrity and associated metabolic and inflammatory pathways.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;IP inhibitor ONX-0914 significantly impacted the intestinal inflammatory microenvironment and gut microbiota of mdx mice. ONX-0914 treatment increased gastrointestinal transit (increased wet/dry faecal weights, &lt;i&gt;p&lt;/i&gt; = 0.0486 and &lt;i&gt;p&lt;/i&gt; = 0.0112, respectively) and partially restored intestinal barrier integrity (reduced FITC-dextran leakage, &lt;i&gt;p&lt;/i&gt; = 0.0449). JAM-A was significantly upregulated (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Colonic CD206+ M2 macrophages increased, while CD68 + M1 cells partially decreased. ONX-0914 downregulated IP isoforms in macrophages (PSMB8: &lt;i&gt;p&lt;/i&gt; = 0.0022; PSMB9: &lt;i&gt;p&lt;/i&gt; = 0.0186) as well as FOXO-1 (&lt;i&gt;p&lt;/i&gt; = 0.0380) and TNF-α (&lt;i&gt;p&lt;/i&gt; = 0.0487). Antibiotic-induced microbiota depletion abrogated these effects. Metagenomic analysis revealed significant differences in microbiota composition between C57Bl controls and mdx mice (PERMANOVA &lt;i&gt;p&lt;/i&gt; &lt; 0.001), with ONX-0914 inducing enrichment of stachyose degradation pathways. Metabolomic analysis showed enrichment of bacterial metabolites, fatty acid and sugar metabolism pathways, with increased glutathione, galactose, glycerol, glyceraldehyde and TCA cycle intermediates. ONX-0914 improved mitochondrial activity in skeletal muscle, as increased expression of ETC complexes (mdx vs. mdx+ONX: Complex II, &lt;i&gt;p&lt;/i&gt; = 0.0338; Complex IV, &lt;i&gt;p&lt;/i&gt; = 0.0023) and TCA enzymes (mdx vs. FTMmdx+ONX: IDH &lt;i&gt;p&lt;/i&gt; = 0.0258; FH &lt;i&gt;p&lt;/i&gt; = 0.0366). This led to a shift towards oxidative muscle fibres and improved muscle morphology (increased fibre size, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 mdx vs. mdx+ONX and mdx vs. FTMmdx+ONX). Muscle performance was enhanced with reduced CPK levels (&lt;i&gt;p&lt;/i&gt; = 0.0015 mdx vs. mdx+ONX) and fibrosis (decreased TGFβ: mdx vs. mdx+ONX, &lt;i&gt;p&lt;/i&gt; = 0.0248; mdx vs. FTMmdx+ONX, &lt;i&gt;p&lt;/i&gt; = 0.0279). ONX-0914 reduced CD68+ (mdx vs. mdx+ONX, &lt;i&gt;p&lt;/i&gt; = 0.0024; mdx vs. FTMmdx+ONX, &lt;i&gt;p&lt;/i&gt; &lt","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle-Specific Strength Better Predicts Physical Performance Decline Than Conventional Metrics: The I-Lan Longitudinal Aging Study","authors":"Wen-Kai Chien,&nbsp;Wei-Ju Lee,&nbsp;Chih-Kuang Liang,&nbsp;Ko-Han Yen,&nbsp;Li-Ning Peng,&nbsp;Ming-Hsien Lin,&nbsp;Ching-Hui Loh,&nbsp;Fei-Yuan Hsiao,&nbsp;Liang-Kung Chen","doi":"10.1002/jcsm.70078","DOIUrl":"10.1002/jcsm.70078","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Muscle-specific strength (MSS), defined as grip strength normalized to arm muscle mass, may better reflect muscle efficiency than grip strength. Despite its potential utility in diagnosing sarcopenia, longitudinal studies evaluating MSS as a predictor of sarcopenia-related outcomes remain limited. This study investigated the associations of MSS with physical performance deterioration and biomarker profiles in community-dwelling older adults, compared it with conventional measures, determined whether MSS-defined sarcopenia offers superior predictive utility versus traditional diagnostic criteria and examined associations with key cardiometabolic and inflammatory biomarkers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective cohort study included 1609 participants (mean age 64.5 ± 6.7 years; 50.5% male) from the I-Lan Longitudinal Aging Study. MSS was calculated by dividing handgrip strength by dominant arm muscle mass. Participants were categorized into low and normal MSS groups using age-sex-specific cutoffs based on quintiles. Physical function was assessed using the five-time chair stand test, with impaired physical performance (PPI) defined as taking ≥ 12 s. Logistic regression models examined the associations between MSS and PPI, adjusted for demographics, comorbidities, cognitive function and skeletal muscle index. Biomarker profiles, including metabolic, inflammatory and hormonal parameters, were compared across MSS groups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Low MSS was found in 19.9% of participants. Those with low MSS had significantly higher muscle mass (skeletal muscle index, 7.7 ± 1.2 vs. 7.1 ± 1.2 kg/m&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; dominant hand muscle mass, 2.7 ± 0.8 vs. 2.3 ± 0.6 kg, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) but weaker grip strength (26.1 ± 8.1 vs. 32.0 ± 8.8 kg, p &lt; 0.001), indicating disproportionately low strength relative to muscle size. PPI was more common in the low MSS group (47.8% vs. 29.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Low MSS was significantly associated with higher odds of PPI (adjusted OR = 1.49, 95% CI: 1.11–1.99, &lt;i&gt;p&lt;/i&gt; = 0.008), particularly among participants aged ≥ 65 years (OR = 1.80, 95% CI: 1.18–2.74, &lt;i&gt;p&lt;/i&gt; = 0.006) and males (OR = 1.64, 95% CI: 1.09–2.47, &lt;i&gt;p&lt;/i&gt; = 0.018). MSS-defined sarcopenia showed a stronger association with PPI (OR = 3.31, 95% CI: 1.26–8.74, &lt;i&gt;p&lt;/i&gt; = 0.015) than conventional sarcopenia definitions. Individuals with low MSS demonstrated adverse metabolic profiles, including higher fasting glucose (101.0 ± 27.3 vs. 95.0 ± 18.7 mg/dL, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), HbA1c (6.0% ± 0.9% vs. 5.8% ± 0.7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and HOMA-IR (2.6","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSE/H2S/SESN2 Signalling Mediates the Protective Effect of Exercise Against Immobilization-Induced Muscle Atrophy in Mice","authors":"Xiuru Li,&nbsp;Yating Huang,&nbsp;Xuege Yang,&nbsp;Sujuan Liu,&nbsp;Yanmei Niu,&nbsp;Li Fu","doi":"10.1002/jcsm.70083","DOIUrl":"10.1002/jcsm.70083","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Hydrogen sulphide (H&lt;sub&gt;2&lt;/sub&gt;S), a gasotransmitter synthesized by cystathionine-γ-lyase (CSE), exhibits antioxidant properties and may mimic exercise-induced muscle protection. However, its mechanistic role in muscle atrophy and exercise intervention remains unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Six-month-old male wild-type (WT) and SESN2 knockout (SESN2&lt;sup&gt;−/−&lt;/sup&gt;) C57BL/6J mice were subjected to a 2-week hindlimb immobilization, followed by combined resistance and aerobic exercise or pharmacological intervention using the H&lt;sub&gt;2&lt;/sub&gt;S donor NaHS (30 μmol/kg) or the CSE inhibitor DL-propargylglycine (PAG, 50 mg/kg). In vitro, C&lt;sub&gt;2&lt;/sub&gt;C&lt;sub&gt;12&lt;/sub&gt; myotubes were treated with H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; and NaHS to assess oxidative stress injury. Muscle mass, cross-sectional area (CSA), collagen deposition and oxidative stress markers were evaluated via histology, Western blot and immunofluorescence.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Compared with the immobilization (IM) group, mice receiving a 2-week combined exercise intervention (IM + EX) exhibited significantly increased gastrocnemius muscle mass/body weight (10.86 ± 0.62 vs. 8.56 ± 1.61, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), enlarged muscle fibre CSA (1628 ± 265 μm&lt;sup&gt;2&lt;/sup&gt; vs. 905.5 ± 88.52 μm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and reduced collagen deposition as indicated by Sirius red staining (collagen-positive area: 2.86% ± 1.12% vs. 7.06 ± 1.18%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Pharmacological inhibition of CSE with PAG significantly attenuated these exercise-induced improvements (muscle mass/body weight: 10.22 ± 0.59, CSA: 1139 ± 96.21 μm&lt;sup&gt;2&lt;/sup&gt;, collagen area: 5.04 ± 0.66%, all &lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. IM + EX). Conversely, administration of the H&lt;sub&gt;2&lt;/sub&gt;S donor NaHS mimicked the protective effects of exercise, increasing muscle mass/body weight (8.94 ± 0.51), CSA (1474 ± 176.1 μm&lt;sup&gt;2&lt;/sup&gt;) and reducing collagen accumulation (collagen area: 3.04 ± 0.74%, all &lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. IM). In vitro, NaHS treatment (30 μM) significantly reversed H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-induced reductions in myotube diameter (19.16 ± 0.91 μm vs. 15.61 ± 0.72 μm, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and improved fusion index (46.47 ± 1.51% vs. 35.28 ± 2.87%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Western blot analysis showed that NaHS upregulated SESN2 and Nrf2 expression, as well as downstream antioxidant proteins HO-1 and NQO1 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), whereas SESN2 knockdown blocked these effects and abolished NaHS-mediated protection in myotubes. In SESN2&lt;sup&gt;−/−&lt;/sup&gt; mice, NaHS failed to increase muscle mass/body weight (7.24 ± 1.3 vs. WT + NaHS 10.12 ± 0.38, &lt;i&gt;p&lt;/i&gt; &lt; 0.","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}