Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Prediagnosis Insights Into Amyotrophic Lateral Sclerosis: Clinical Symptoms and Medication Use","authors":"Chunyang Pang,&nbsp;Wen Cao,&nbsp;Jiali Xie,&nbsp;Yaojia Li,&nbsp;Luyi Zhu,&nbsp;Huan Yu,&nbsp;Dongsheng Fan,&nbsp;Binbin Deng","doi":"10.1002/jcsm.70003","DOIUrl":"https://doi.org/10.1002/jcsm.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyotrophic lateral sclerosis (ALS) has a prolonged latency period, though its preclinical characteristics remain poorly understood. This study uses UK Biobank data to explore and compare ALS's pre-diagnostic features, including symptoms and medication use, aiming to provide insights into the disease's underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical symptoms and medications were identified from self-reports, hospital records, and death registry data. Propensity score matching was used to match ALS with Alzheimer's disease (<span>AD</span>) and Parkinson's disease (PD), ensuring balance in socioeconomic factors to compare symptoms 0–5 years before diagnosis. Cox regression analysis was applied to assess the associations between medication use and the risk of incident ALS and mortality after ALS diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 753 ALS cases were observed in 502 417 participants, with an incidence rate of 10.58 per 100 000 person-years. In the ALS cohort, the male-to-female ratio was 2.9, with a median age at onset of 64.61 years (Interquartile range (IQR): 56.80–71.31) and a median survival time post-diagnosis of 9.08 months (IQR: 3.18–18.98), while females (log-rank <i>p</i> = 0.038) and individuals with earlier (&lt; 64.61 years) disease onset (log-rank <i>p</i> &lt; 0.001) had longer survival periods. In the 5 years prior to diagnosis, ALS showed a higher incidence of falls compared to <span>ad</span> (11.3% vs. 3.2%, <i>p</i> &lt; 0.001), but a lower incidence than PD (10.7% vs. 28.3%, <i>p</i> &lt; 0.001). Additionally, ALS had a lower incidence of depression (4.6% vs. 25.6%, <i>p</i> &lt; 0.001), anxiety (3.5% vs. 18.1%, <i>p</i> &lt; 0.001), sleep disorders (1.4% vs. 7.2%, <i>p</i> &lt; 0.001), hypotension (3.4% vs. 30.5%, <i>p</i> &lt; 0.001), constipation (0.3% vs. 4.9%, <i>p</i> &lt; 0.001), and urinary dysfunction (2.2% vs. 8.7%, <i>p</i> &lt; 0.001) compared with PD. The use of calcium channel blockers may be a risk factor for incident ALS (adjusted HR 1.61, 95% CI: 1.22–2.12, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pre-diagnostic presentations of falls are more frequent in ALS than in <span>AD</span>, but less frequent than in PD. However, ALS exhibits fewer psychiatric symptoms and autonomic dysfunction compared with PD. The use of calcium channel blockers may be associated with an increased risk of developing ALS in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598447","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":"Global Burden of Musculoskeletal Disorders in Adults Aged 50 and Over, 1990–2021: Risk Factors and Sociodemographic Inequalities","authors":"Shi-Yang Guan,&nbsp;Jin-Xin Zheng,&nbsp;Shun-Xian Zhang,&nbsp;Shengqian Xu,&nbsp;Zongwen Shuai,&nbsp;Hong-Yan Cai,&nbsp;Faming Pan","doi":"10.1002/jcsm.70008","DOIUrl":"https://doi.org/10.1002/jcsm.70008","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;Adults aged 50 and over are particularly vulnerable to musculoskeletal (MSK) disorders, with their impact expected to intensify as the global population ages. This study aims to comprehensively assess the global burden of MSK disorders among adults aged 50 and over from 1990 to 2021, as well as temporal trends, risk factors and sociodemographic inequalities.&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;Data were sourced from the Global Burden of Disease 2021 study. Temporal trends in age-standardized rates were evaluated by calculating average annual percent changes (AAPC). Absolute and relative inequalities were assessed using the slope index of inequality and concentration index, respectively.&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;From 1990 to 2021, MSK disorders remained the largest contributor to total years lived with disability (YLDs) among adults aged 50 and over globally. The global age-standardized incidence rate significantly decreased (AAPC = −0.181, 95% CI: −0.190 to −0.172), whereas the global prevalence and disability-adjusted life-year (DALY) rates significantly increased (AAPC = 0.126, 95% CI: 0.118–0.134, and AAPC = 0.057, 95% CI: 0.042–0.072, respectively). High sociodemographic index (SDI) countries exhibited the highest age-standardized incidence, prevalence and DALY rates (11 236.6, 56 308.1 and 5277.1 per 100 000 population, respectively), whereas low-middle SDI countries showed the most rapid increases in prevalence and DALY rates (AAPC = 0.229, 95% CI: 0.218–0.240, and AAPC = 0.230, 95% CI: 0.204–0.256, respectively). Significantly positive associations were identified between SDI and age-standardized incidence, prevalence and DALY rates (all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). High body mass index (BMI) was the largest contributor to global DALYs of MSK disorders, accounting for 10.3% of the total in this population, whereas occupational ergonomic factors, smoking and kidney dysfunction contributed 7.3%, 6.0% and 0.2%, respectively. Although the proportions of DALYs due to occupational ergonomic factors and smoking declined globally (from 9.2% to 7.3% and from 8.9% to 6.0%, respectively), those due to high BMI and kidney dysfunction increased (from 7.7% to 10.3% and from 0.19% to 0.22%, respectively). Both absolute and relative SDI-related inequalities persisted across 204 countries and territories, with no significant changes observed.&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;MSK disorders have remained the largest contributor to disability among adults aged 50 and over. Despite ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589804","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-Specific Deletion of E3 Ligase Asb2 Enhances Muscle Mass and Strength","authors":"Hye Rim Jang,&nbsp;Shi-Young Park,&nbsp;Yeonmi Lee,&nbsp;Dongjin Lee,&nbsp;Jongjun Lee,&nbsp;Yoonil Cho,&nbsp;Cheol Soo Choi,&nbsp;Hui-Young Lee","doi":"10.1002/jcsm.70007","DOIUrl":"https://doi.org/10.1002/jcsm.70007","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;Maintaining skeletal muscle mass and strength is crucial to prevent sarcopenia during healthy ageing. Ankyrin repeat and suppressor of cytokine signalling box protein 2 (&lt;i&gt;Asb2&lt;/i&gt;), an E3 ligase, has been implicated in regulating muscle mass; however, its roles on muscle strength remain unclear, with mixed findings from previous studies. Overexpression of &lt;i&gt;Asb2&lt;/i&gt; decreases muscle mass, whereas its knockdown delays myoblast differentiation and reduces contractile proteins. Given these contradictory findings, we aimed to clarify the role of &lt;i&gt;Asb2&lt;/i&gt; in muscle mass and strength using a skeletal muscle-specific &lt;i&gt;Asb2&lt;/i&gt; knockout (&lt;i&gt;Asb2&lt;/i&gt; MKO) mouse model. Additionally, we investigate the long-term effects of &lt;i&gt;Asb2&lt;/i&gt; on aged muscle, underlying mechanisms on muscle regulation and metabolic effects of &lt;i&gt;Asb2&lt;/i&gt; MKO mice to better understand its role in muscle function and age-related metabolic diseases.&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;&lt;i&gt;Asb2&lt;/i&gt; MKO mice were generated using &lt;i&gt;Acta1&lt;/i&gt;-Cre recombinase. Body composition was quantified in male and female mice up to 18 months of age. Muscle strength, energy expenditure and glucose metabolism were evaluated using the grip strength test, mitochondrial oxygen consumption measurement, indirect calorimetry and glucose/insulin tolerance tests. Transcriptomic analyses and siRNA studies were performed to elucidate the mechanisms underlying the &lt;i&gt;Asb2&lt;/i&gt; deletion.&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 MKO mice were born healthy and exhibited selective &lt;i&gt;Asb2&lt;/i&gt; deletion in the skeletal muscle, leaving the cardiac muscle unaffected. This deletion led to an increase in the mass of various skeletal muscles (9%–23%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and improved grip strength (~10%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), both of which were sustained throughout the ageing process. The MKO mice also revealed enhanced mitochondrial function, energy expenditure and whole-body insulin sensitivity. Transcriptomic data supported the muscle phenotype observed in the MKO mice. Notably, desmin, a protein critical for structural integrity and mitochondrial function, was identified as a target protein of the ASB2 E3 ligase.&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;Skeletal muscle-specific deletion of &lt;i&gt;Asb2&lt;/i&gt; led to increased muscle mass and strength, potentially through preservation of desmin levels. These findings suggest that targeting &lt;i&gt;Asb2&lt;/i&gt; may enhance muscle growth and prevent age-related muscle decline, with potential benefits for metabolic health","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598574","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":"EIF4A3 Promotes Muscle Atrophy and Aging by Inhibiting the FAK Pathway Through NEDD9 mRNA Destabilization","authors":"Qian Li,&nbsp;Xiaohang Yin,&nbsp;Wensi Wan,&nbsp;Yi Zhou,&nbsp;Siqi Wang,&nbsp;Yuwei Yan,&nbsp;Jingying Chen,&nbsp;Xinyi Ren,&nbsp;Junli Gao,&nbsp;Yuying Chen,&nbsp;Yanan Zhang,&nbsp;Caiyue Cui,&nbsp;Emeli Chatterjee,&nbsp;Guoping Li,&nbsp;Ming Wu,&nbsp;Yan Zhang,&nbsp;Dongchao Lu,&nbsp;Tingting Yang,&nbsp;Yongjun Zheng,&nbsp;Jin Li","doi":"10.1002/jcsm.70010","DOIUrl":"https://doi.org/10.1002/jcsm.70010","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 atrophy has a poor prognosis, caused by various factors. Identifying a shared treatment target could address an unmet clinical need. The exon junction complex (EJC), a protein complex assembly that binds to RNA, facilitates post-transcriptional regulation by participating in mRNA splicing, mRNA export, translation and nonsense-mediated mRNA decay. This study aims to investigate the role of the EJC in muscle atrophy.&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;Single-cell transcriptome analysis and western blot were employed to analyse EJC expression in muscle atrophy. Overexpression of EJC helicase EIF4A3, as well as counteracting endogenous EIF4A3, was manipulated using lentiviral and adeno-associated virus 8 (AAV8) at both in vitro and in vivo levels. Imaging, RT-qPCR and immunoblot were utilized to identify phenotypes associated with muscle atrophy and aging. RNA-seq, RIP-seq, RT-qPCR and RIP-PCR were conducted to determine the targets of EIF4A3. A pharmacological approach that activates the downstream pathways in EIF4A3 knockdown muscle was employed to elucidate the molecular mechanisms of EIF4A3 in muscle atrophy.&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 core RNA helicase of the EJC, EIF4A3, showed increased expression in atrophied muscles and aging human muscle (+150.43%, &lt;i&gt;n&lt;/i&gt; = 5 in young and aged human, age: 26.20 ± 6.760 vs. 73.60 ± 5.030, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and aged mice muscle (+74.54% in male, +61.28% in female: &lt;i&gt;n&lt;/i&gt; = 6 in young and aged mice in male/female, age: 3 months vs. 20 months, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In vitro studies demonstrated that EIF4A3 overexpression promoted muscle atrophy and aging in myotubes (&lt;i&gt;n&lt;/i&gt; = 6, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), while EIF4A3 inhibition mitigated these effects (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In vivo phenotypic analysis indicated that overexpression of EIF4A3 in skeletal muscle promoted muscle atrophy (&lt;i&gt;n&lt;/i&gt; = 10, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) including reduced grip strength (−42.36%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), running capacity (−21.24%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), contraction force (−19.62%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), muscle weight (gastrocnemius muscle: −15.75%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001; tibialis anterior muscle: −9.50%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), myofiber size (−11.59%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and worsened molecular phenotypes (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Knockdown of EIF4A3 protected against muscle atrophy induced by various stimuli, including denervation (&lt;i&gt;n&lt;/i&gt; = 10, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), immobilization (&lt;i&gt;n&lt;/i&gt; = 10, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and angiotensin II (&lt;i&gt;n&lt;/i&gt; = 6–10, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) in mice. Mechanistically, Neural Precursor Cell Expressed, Developmentally Down-Regulat","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598571","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":"Impaired Autophagic Flux in Skeletal Muscle of Plectin-Related Epidermolysis Bullosa Simplex With Muscular Dystrophy","authors":"Michaela M. Zrelski,&nbsp;Margret Eckhard,&nbsp;Petra Fichtinger,&nbsp;Sabrina Hösele,&nbsp;Andy Sombke,&nbsp;Leonid Mill,&nbsp;Monika Kustermann,&nbsp;Wolfgang M. Schmidt,&nbsp;Fiona Norwood,&nbsp;Ursula Schlötzer-Schrehardt,&nbsp;Gerhard Wiche,&nbsp;Rolf Schröder,&nbsp;Lilli Winter","doi":"10.1002/jcsm.70001","DOIUrl":"https://doi.org/10.1002/jcsm.70001","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;Plectin, a multifunctional cytolinker and intermediate filament stabilizing protein, is essential for muscle fibre integrity and function. Mutations in the human plectin gene (&lt;i&gt;PLEC&lt;/i&gt;) cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). The disorganization and aggregation of desmin filaments in conjunction with degenerative changes of the myofibrillar apparatus are key features in the skeletal muscle pathology of EBS-MD. We performed a comprehensive analysis addressing protein homeostasis in this rare protein aggregation disease by using human EBS-MD tissue, plectin knock-out mice and plectin-deficient cells.&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;Protein degradation pathways were analysed in muscles from EBS-MD patients, muscle-specific conditional plectin knockout (MCK-Cre/cKO) mice, as well as in plectin-deficient (&lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt;) myoblasts by electron and immunofluorescence microscopy. To obtain a comprehensive picture of autophagic processes, we evaluated the transcriptional regulation and expression levels of autophagic markers in plectin-deficient muscles and myoblasts (RNA-Seq, qRT-PCR, immunoblotting). Autophagic turnover was dynamically assessed by measuring baseline autophagy as well as specific inhibition and activation in mCherry-EGFP-LC3B-expressing &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; myoblasts, and by monitoring primary &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; myoblasts using organelle-specific dyes. Wild-type and MCK-Cre/cKO mice were treated with chloroquine or metformin to assess the effects of autophagy inhibition and activation in vivo.&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;Our study identified the accumulation of degradative vacuoles as well as LC3- and SQSTM1-positive patches in EBS-MD patients, MCK-Cre/cKO mouse muscles and &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; myoblasts. The transcriptional regulation of ~30% of autophagy-related genes was altered, and protein levels of downstream targets of the autophagosomal degradation machinery were elevated in MCK-Cre/cKO muscle lysates (e.g., LAMP2, BAG3 and SQSTM1 to ~160, ~150 and ~140% of controls, respectively; &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Autophagosome turnover was compromised in mCherry-EGFP-LC3B-expressing &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; myoblasts (~40% reduction in median red:green ratio, reduced puncta number, smaller puncta; &lt;i&gt;p&lt;/i&gt; &lt; 0.01). By labelling autophagic compartments with CYTO-ID dye or lysosomes with LYSO-ID, we found reduced signal intensities in primary &lt;i&gt;Plec&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; cells (&lt;i","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598372","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":"Late-Stage Skeletal Muscle Transcriptome in Duchenne Muscular Dystrophy Shows a BMP4-Induced Molecular Signature","authors":"Hanna Sothers,&nbsp;Xianzhen Hu,&nbsp;David K. Crossman,&nbsp;Ying Si,&nbsp;Matthew S. Alexander,&nbsp;Merry-Lynn N. McDonald,&nbsp;Peter H. King,&nbsp;Michael A. Lopez","doi":"10.1002/jcsm.70005","DOIUrl":"https://doi.org/10.1002/jcsm.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function variants in the <i>DYSTROPHIN</i> gene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of the TGFβ family of cytokines, like TGFβ1 and BMP4. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation of <i>Smad8</i> transcription in muscle cells. However, the role of BMP4 in late-stage DMD skeletal muscle is unknown. We hypothesized that BMP4 signalling is a driver of aberrant gene expression in late-stage human DMD skeletal muscle detectable by a transcriptomic signature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptomes from skeletal muscle biopsies of late-stage DMD versus non-DMD controls and C2C12 muscle cells with or without BMP4 stimulation were generated using RNA-Seq. We tested transcriptional differences at the single transcript level in skeletal muscle biopsy samples from three patients with DMD and compared them to three non-DMD. They were then analyzed by Ingenuity Pathway Analysis, weighted gene coexpression network analyses (WGCNA) and Gene Set Enrichment Analysis (GSEA). Key hub and high-fold change genes overlapping in the DMD and BMP4 muscle transcriptomes were validated in additional primary and bulk skeletal muscle samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3048 transcripts in the human muscle and 5291 transcripts in C2C12 muscle cells were differentially expressed. WGCNA identified an overlapping molecular signature of 1027 genes dysregulated in DMD muscle that were induced in BMP4-stimulated C2C12 muscle cells. <i>SERPING1</i> and <i>Aff3</i> were identified as the top hub genes. Highly upregulated DMD muscle transcripts that overlapped with BMP4-stimulated C2C12 muscle cells included <i>ADAM12</i>, <i>SERPING1</i>, <i>SMAD8</i> and <i>SFRP4</i>. DMD skeletal muscle analysis showed aberrant upregulation of TGFβ signalling, extracellular matrix remodelling and collagen biosynthesis pathways, in contrast to inhibited mitochondrial and metabolic pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, the DMD transcriptome was characterized by dysregulation of immune function, ECM remodelling and muscle bioenergetic metabolism. We additionally define a late-stage DMD skeletal muscle transcriptome that overlaps with a BMP4-induced molecular signature in C2C12 muscle cells. This supports BMP4/Smad8 pathway as a disea","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598572","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 Adipose Tissue and Lipids on Skeletal Muscle in Sarcopenia","authors":"Soo Yeon Jang,&nbsp;Kyung Mook Choi","doi":"10.1002/jcsm.70000","DOIUrl":"https://doi.org/10.1002/jcsm.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the decline in muscle mass, function and increased visceral obesity are attracting substantial attention in the ageing society, approved treatment modalities for sarcopenia/sarcopenic obesity (SO) remain limited. Elucidating effects and mechanisms of adipose tissue and lipids on skeletal muscle is important for identifying potential prevention and treatment targets for sarcopenia/SO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review, we aim to comprehensively summarize current knowledge on how adipose tissue and lipid metabolites influence skeletal muscle with detailed mechanistic explanations, especially in sarcopenia development. We also tried to explore future perspectives for optimal strategies for managing sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fatty infiltration in skeletal muscle can alter the structure, metabolism and signalling pathways of muscle, thereby worsening muscle function and physical performance. Intracellular lipid droplets could disrupt normal physiology within muscle cells, but it might be influenced not only by quantity but also by size, location and characteristics of lipid droplets. Intracellular lipid metabolites may induce lipotoxicity in cell signalling of muscle cells, but effects might differ by types or chemical structure. Highly trained athletes exhibit insulin sensitivity despite high levels of muscular fat, a phenomenon called the athlete's paradox. Lipid droplets within the skeletal muscle of athletes are small and are mainly located in the intermyofibrillar area, which is rich in fast-twitch, Type I fibres. In contrast, patients with Type 2 diabetes/obesity accumulate larger lipid droplets in the subsarcolemmal area, which is richer in Type II fibres. Ageing is intricately associated with mitochondrial dysfunction and the concomitant decline in mitochondrial biogenesis, all of which may lead to sarcopenia. SIRT1 and AMPK, two key energy sensors, are involved in mitochondrial biogenesis through regulation of PGC-1<i>α</i>. Modulation of PGC-1<i>α</i> levels in skeletal muscle may help protect against sarcopenia by preserving muscle integrity, enhancing muscle function, improving insulin sensitivity and reducing inflammation and oxidative stress. Excessive nutrient intake and obesity triggers mitochondrial dysfunction by inducing activation of the inflammatory response and increased production of reactive oxygen species. Skeletal muscle and adipose tissue are closely connected through mediators called adipokines and myokines, and it is important to understand the mechanisms of their interaction.</p>\u0000 </section>\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598573","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":"Correction to “Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta-Analysis”","authors":"","doi":"10.1002/jcsm.13875","DOIUrl":"https://doi.org/10.1002/jcsm.13875","url":null,"abstract":"<p>\u0000 <span>Wan, R.</span>, <span>Huang, J.</span>, <span>Wang, K.</span>, <span>Long, D.</span>, <span>Tao, A.</span>, <span>Huang, J.</span> and <span>Liu, Z.</span> (<span>2025</span>), <span>Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta-Analysis</span>. <i>Journal of Cachexia, Sarcopenia and Muscle</i>, <span>16</span>: e13806, https://doi.org/10.1002/jcsm.13806.\u0000 </p><p>In the “Results” section of the Abstract, the text: “Nine eligible RCTs with 1838 participants were included in this study” was incorrect. This should have read: “Nineteen eligible RCTs with 1838 participants were included in this study”. The correct number reflects the total studies included in our meta-analysis (19, not 9). This does not affect the overall conclusions, data integrity, or reproducibility of the study.</p><p>We apologize for this error.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581921","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":"Novel Algorithm to Estimate Fat-Free Muscle Volumes in Women Using the Urinary Deuterated-Creatine Dilution Method","authors":"Darren Yuen Zhang Tan,&nbsp;Wei Fun Cheong,&nbsp;Shanshan Ji,&nbsp;Amaury Cazenave-Gassiot,&nbsp;Jane Cauley,&nbsp;Liang Shen,&nbsp;Eu-Leong Yong","doi":"10.1002/jcsm.13872","DOIUrl":"https://doi.org/10.1002/jcsm.13872","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D₃Cr) dilution method provides a direct assessment of muscle mass, but its accuracy in Asian women has not been evaluated. Our aim was to develop a new D₃Cr algorithm incorporating anthropomorphic variables that can estimate fat-free muscle mass, using magnetic resonance imaging (MRI) as the reference standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community-dwelling women, aged 45–69 years at baseline, who attended gynaecological clinics from 2014 to 2016. Between February 2021 and July 2023, 894 participants were recontacted, and 451 of the respondents agreed to ingest 30 mg of D₃Cr and had available MRI measurements of fat-free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D₃-creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D₃Cr. Muscle mass was estimated using the two D₃Cr algorithms (D₃Cr_original and D₃Cr_modified) in current use and a newly developed algorithm (D₃Cr_Ht-Wt) incorporating anthropometric variables that estimate fat-free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D₃Cr algorithms with MRI. Bland–Altman analysis was used to ascertain agreement between D₃Cr_Ht-Wt and MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants (<i>n</i> = 451, mean age 62.6 ± 5.9) were randomly divided into training (<i>n</i> = 367) and validation (<i>n</i> = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (<i>β</i> = −0.011, <i>p</i> = 0.076) and ethnicity (<i>β</i> = 0.154, <i>p</i> = 0.317 [Indian]; <i>β</i> = −0.012, <i>p</i> = 0.942 [Malay] compared to Chinese) were not associated with fat-free muscle volumes. In the final model, D₃Cr-determined creatine pool size (<i>β</i> = 0.032, <i>p</i> &lt; 0.001), body weight (<i>β</i> = 0.030, <i>p</i> &lt; 0.001) and height (<i>β</i> = 4.336, <i>p</i> &lt; 0.001) were independently associated with fat-free muscle volumes and were incorporated into a new algorithm (D₃Cr_Ht-Wt). In a separate validation cohort, muscle volumes estimated using the D₃Cr_Ht-Wt algorithm (<i>R</i> = 0.813) had a higher correlation with MRI-measured fat-free muscle volumes than both D<sub","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582074","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":"Integrating Body Composition and Nutritional Indices: A Novel Prognostic Tool for Survival in Pancreatic Cancer","authors":"Yiting Xu,&nbsp;Yang Chen,&nbsp;Gaowei Jin,&nbsp;Chenrui Yao,&nbsp;Yangyang Wang,&nbsp;Ziyang Wei,&nbsp;Zhihang Cai,&nbsp;Xuanhao Gu,&nbsp;Binbin Deng,&nbsp;Peilu Wang,&nbsp;Yuxiong Feng,&nbsp;Qi Zhang,&nbsp;Tingbo Liang","doi":"10.1002/jcsm.70006","DOIUrl":"https://doi.org/10.1002/jcsm.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia and malnutrition have been independently associated with a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), but their combined association with patient outcomes is not fully understood. This study aimed to systematically evaluate the synergistic effects of body composition parameters and nutritional index as prognostic indicators in patients with PDAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 596 patients with PDAC who underwent surgical resection from two centres were initially enrolled in this retrospective study. Body composition parameters, including the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and skeletal muscle density (SMD), were assessed using a single cross-sectional image at the L3 level from preoperative computed tomography scans. The prognostic nutritional index (PNI) was used to assess nutritional status. The combined indices were defined as body composition parameters multiplied by PNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 463 patients were finally included in the analysis, with 339 in the training cohort and 124 in the validation cohort. The median (interquartile) age was 66 (60–72) years, and 274 (59.2%) were male. The median values of SMI, SATI, VATI, SMD, as well as the combined indices of these parameters with PNI, varied significantly by sex in the training cohort. Patients were categorized into sex-specific quartiles (Q1 to Q4) based on SMI × PNI levels. Both overall survival (OS) and disease-free survival (DFS) exhibited significant differences across these quartiles (<i>p</i> &lt; 0.001). Though all body composition parameters and their combinations with PNI were independent predictors of OS in multivariate analysis, the combination of SMI × PNI demonstrated superior prognostic performance compared to other indices (c-statistics: 0.767, AICc: 1648.8). These results remained consistent across stratified analysis. The external validation cohort confirmed that SMI × PNI exhibited enhanced predictive and discriminative power compared with other indices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SMI × PNI represents a robust and accessible prognostic tool for assessing survival in patients with PDAC. Further prospective studies are needed to validate its effectiveness across diverse populations and clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581920","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}