Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Characterization of Muscle Tissue Cell Diversity and Clinical Implications in Idiopathic Inflammatory Myopathy","authors":"Honglin Zhu, Yizhi Xiao, Shasha Xie, Qiming Meng, Ting Ding, Ting Huang, Di Liu, Sijia Liu, Xiaoli Zhang, Huali Zhang, Hui Luo","doi":"10.1002/jcsm.70043","DOIUrl":"https://doi.org/10.1002/jcsm.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Idiopathic inflammatory myopathies (IIMs) exhibit diverse cellular microenvironments in muscle tissues, yet the full spectrum of cell populations and changes remains unclear. This study aimed to characterize cellular heterogeneity, explore cell–cell interactions and assess the prognostic value of cell subtype abundances across IIM subtypes in Han Chinese.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Muscle samples from six IIMs and three normal controls (NC) underwent single-cell RNA sequencing (scRNA-seq), whereas bulk RNA sequencing was performed on 203 IIMs and 19 NC. To avoid potential biases in cell proportion data from scRNA-seq, we used CIBERSORTx, a robust deconvolution method, to estimate cell subtype abundances in the large IIMs cohort. Cell–cell interaction, correlation and survival analysis were performed to investigate associations between cell subtypes, clinical features and disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 10 T/NK cell types, eight monocyte/macrophage/dendritic cell types, 10 vascular-related cell types and four skeletal muscle cell types in IIM muscle tissues, with varying abundances across subgroups. Increased ISG<sup>hi</sup> T cells (1.42% vs. 0.075% in NC) and ISG<sup>hi</sup> monocytes (4.24% vs. 0% in NC) in dermatomyositis (DM), particularly in anti-MDA5 and anti-NXP2 patients, correlated with skin rashes and higher relapse rates. CD56<sup>dim</sup>CD16<sup>dim</sup>NK cells, exhibiting the highest cytotoxicity, were elevated most in anti-SRP (11.93% vs. 8.15% in NC) immune-mediated necrotizing myopathy (IMNM) and associated with severe muscle damage (<i>p</i> = 0.0001, rho = 0.267). Reduced angiogenesis-related SERPINB2<sup>+</sup> monocytes (37.12% vs. 46.69% in NC) predicted better outcomes in IMNM (<i>p</i> = 0.006, HR = 0.264), whereas decreased HIF3A<sup>+</sup>CECs (14.29% in DM vs. 16.95% in NC), essential for endothelial barrier maintenance, negatively correlated with myofiber necrosis (<i>p</i> = 0.016, rho = −0.168) and were predictive of improved outcomes in DM (<i>p</i> = 0.014, HR = 0.412). Elevated endothelial-like pericytes in antisynthetase syndrome (ASS, 55.34% vs. 50.02% in NC) and IMNM (54.42%) were linked to muscle damage (<i>p</i> < 0.0001, rho = 0.272). Certain key pathways, such as angiogenesis-related pathways, were linked to better outcomes in DM (<i>p</i> = 0.002, HR = 0.405), whereas increased cytotoxicity scores, cell chemotaxis and regulation of inflammatory response were associated with a higher risk of relapse in both DM and IMNM. We also observed a reduction in Type I muscle fibres (22.66% in ASS vs. 66","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144909975","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":"A Comparative Analysis of Grip Strength Evaluation Methods in a Large Cohort of Aged Mice","authors":"Giorgia Bigossi, Serena Marcozzi, Maria Elisa Giuliani, Giovanni Lai, Beatrice Bartozzi, Fiorenza Orlando, Laura Gerosa, Amir Mohammad Malvandi, Diana Putavet, Esmée Bouma, Peter L. J. de Keizer, Giovanni Lombardi, Marco Malavolta","doi":"10.1002/jcsm.70050","DOIUrl":"https://doi.org/10.1002/jcsm.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Grip strength is a key functional marker of musculoskeletal aging, widely used to assess sarcopenia. In preclinical research, multiple measurement methods are often combined to enhance reliability, but standardization remains challenging. To improve measurement robustness, we previously developed a composite strength score (SS5) that integrates five different grip strength tests into a single variable. While SS5 provides a comprehensive evaluation, its implementation is time-consuming, limiting feasibility in large-scale studies. In this study, we also examine two simplified composite scores, SS2 and SS3, as potential streamlined alternatives. Additionally, although normalizing grip strength to body weight is widely used, its appropriateness in geriatric mouse models has never been formally validated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forelimb grip strength was assessed in a cohort of 160-aged C57BL/6J mice using five methods: Weight Lift Tests (Deacon protocol with sponge weights and a modified version with metal wire weights), the Cage Lift Test and the Grip Strength Meter (trapeze bar and grid). Additionally, a cross-sectional group of 173 mice was analysed to assess the correlation between grip strength and muscle size. Each method was evaluated for its correlation with age, ability to detect sex differences, variability and association with muscle size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All methods strongly correlated with age (−0.518 ≤ r<sub>s</sub> ≤ −0.306). The Grip Strength Meter (trapeze bar) and modified Deacon method were the most effective in detecting sex differences (<i>p</i> < 0.001). While all methods correlated with muscle size (0.153 ≤ r<sub>s</sub> ≤ 0.332), the modified Deacon method and Grip Strength Meter showed the strongest associations. The mean coefficient of variation (CV%) ranged from 7% to 17%, demonstrating good repeatability. Notably, despite being widely used, normalization of grip strength to body weight was found to introduce bias in geriatric mice, as age-related weight loss distorts strength assessments. Absolute values proved to be a more reliable measure. To improve efficiency while maintaining reliability, we developed two new composite scores (SS2 and SS3) by integrating a subset of methods from SS5. These scores preserved the strong correlation with age observed in SS5 while reducing the number of required tests, enhancing feasibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Combining multiple grip strength assessments improves me","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910159","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":"Mitochondrial Dysfunction Contributes to Sustained Muscle Loss After Cardiac Surgery: A Prospective Observational Study","authors":"Ashley N. Thomas, Antonis Kalakoutas, Martin Yates, John Yap, Julie Sanders, Paul Kemp, Mark J. D. Griffiths","doi":"10.1002/jcsm.70051","DOIUrl":"https://doi.org/10.1002/jcsm.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, <i>n</i> = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, <i>n</i> = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, <i>n</i> = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: <i>r</i> = 0.58 [95% CI 0.19 to 0.81] <i>p</i> = 0.005) and strength of knee extension (<i>r</i> = 0.54 [95% CI 0.14 to 0.79] <i>p</i> = 0.010) and handgrip (<i>r</i> = 0.63 [95% CI 0.27 to 0.83] <i>p</i> = 0.002: <i>n</i> = 22). Both pre-operative and peak (Day 3) plasma levels of short-chain acyl-carnitine markers of mitochondrial dysfunction correlated with proportional muscle loss at follow-up and with strength at all timepoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Prolonged follow-up after aortic surgery demonstrated a divergence between the consistent recovery of strength and a significant proportion of patients continui","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888312","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":"Reduced Muscle Loss in Patients With NSCLC Taking Fibrates: Findings From a Retrospective Observational Study","authors":"Rahmi Elahjji,&nbsp;Tahj Blow,&nbsp;Rahul Grover,&nbsp;Maurice A. Hurd,&nbsp;Richard F. Dunne,&nbsp;Bette J. Caan,&nbsp;Elizabeth M. Cespedes Feliciano,&nbsp;Andrew J. Plodkowski,&nbsp;James H. Flory,&nbsp;Marcus D. Goncalves","doi":"10.1002/jcsm.70016","DOIUrl":"https://doi.org/10.1002/jcsm.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cancer-anorexia-cachexia syndrome (CACS) is a common and debilitating wasting disorder characterized by loss of skeletal muscle and worse morbidity and mortality. In pre-clinical studies, CACS is associated with loss of peroxisome proliferator-activated receptor alpha (PPAR-α) dependent ketone production in the liver. Fibrates are PPAR-α agonists that are commonly used to treat dyslipidemia. Treating mice with fibrates was found to prevent skeletal muscle loss. We examine whether patients with cancer treated with PPAR-α agonists experience less CACS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective cohort study of patients (<i>N</i> = 6922) at Memorial Sloan Kettering Cancer Center who were diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2017 and were incidentally prescribed fenofibrate or gemfibrozil at the time of diagnosis. These patients were compared to a propensity score-matched control set who were not taking either drug. The primary outcome included a composite outcome of CACS, which included significant weight loss before or after the time of diagnosis. Secondary outcomes included change in cross-sectional skeletal muscle area over time as measured in serial CT imaging studies and overall survival. Descriptive statistics, Kaplan–Meier analysis and multivariable logistic regression were performed to compare outcomes between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among patients with NSCLC, 149 were taking fenofibrate or gemfibrozil at the time of diagnosis. A 2:1 propensity score-matched cohort of 298 patients was created that was well-matched with regard to baseline characteristics. Regarding the primary composite outcome, there was no significant difference in the prevalence of CACS between those taking fibrates and propensity-matched controls (49.7 vs. 46.6%). When skeletal muscle mass was measured directly using cross-sectional imaging, patients on fibrates were found to have lost significantly less muscle area over time (−3.3 vs.−4.2%, <i>p</i> = 0.03). There was no difference in overall survival between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with NSCLC taking fibrates at the time of diagnosis lost less muscle area over time. In a secondary analysis, this change was not associated with a change in overall survival, though this study was likely underpowered for this analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881318","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":"Beyond Body Mass Index: The Impact of Height and Height-Normalised Weight on Overall Survival of Lung Cancer Undergoing Surgery","authors":"Lorenzo Gherzi,&nbsp;Mathilde Prieto,&nbsp;Antonio Iannelli,&nbsp;Laurent Brouchet,&nbsp;Pierre-Benoit Pagès,&nbsp;Pierre Emmanuel Falcoz,&nbsp;Françoise Le Pimpec Barthes,&nbsp;Pascal Alexandre Thomas,&nbsp;Marcel Dahan,&nbsp;Marco Alifano","doi":"10.1002/jcsm.70049","DOIUrl":"https://doi.org/10.1002/jcsm.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Unlike most malignancies, increased adiposity, as expressed by a higher body mass index (BMI), is associated with improved prognosis after lung cancer surgery at the population level. Height, one of the determinants of BMI, is associated with better survival, independent of other confounders, even though BMI is calculated as weight divided by height squared. The association of weight with survival is difficult to assess because, at the individual level, weight is closely linked to height and does not directly reflect adiposity. In this study, we examined the impact of height and weight on overall survival in a large population of patients undergoing upfront surgery for lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We extracted data on all consecutive patients with stage I–IIIA non-small cell lung cancer included in a surgical nationwide dataset over a 16-year period. For each sex, height was categorised in sex-specific quartiles (sH). Sex-specific height-normalised weight (sHNW) was defined as the ratio of an individual's weight to the mean weight of individuals of the same sex and height, and it was categorised into quartiles. Finally, the sum of the category membership (ranging from 1 to 4 according to quartiles) of sH and sHNW was calculated, and the results were categorised into four groups of sH/sHNW. Overall survival (OS) was assessed by Kaplan–Meier, and differences evaluated by log-rank. Cox models were built.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 50 653 patients. Mean age was 65.61 ± 9.45 and 31.99% were women. sH predicted OS, taller height being protective [crude HRs of second, third, and fourth quartiles vs. first quartile: 0.94 (95% CI 0.91–0.98), 0.89 (0.86–0.92), 0.77 (0.74–0.81); <i>p</i> &lt; 0.0001]. sHNW was also associated with OS, with lower sHNW category being associated with worse outcome and higher sHNW categories being protective [crude HRs of second, third and fourth quartiles vs. first quartile: 0.88 (0.85–0.92), 0.82 (0.79–0.85), 0.85 (0.81–0.88); <i>p</i> &lt; 0.0001]. The four classes of sH/sHNW showed higher differences in prognosis with respective crude HRs of 0.88 (0.84–0.93), 0.76 (0.73–0.80) and 0.70 (0.66–0.74) in the intermediate lower, intermediate higher and higher class as compared with the lower class. Five-year overall survival rates were 58.65% (56.89–60.45), 62.96% (62.15–63.78), 67.71% (67.02–68.41) and 70.12% (68.98–71.26), in the lower, intermediate lower, intermediate higher and higher class, respectively. All Cox models showed that sHNW and sH/sHNW predicted survival independently from common confounders.</p>\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869246","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":"High-Density Lipoprotein-Associated Cholesterol Abnormalities in a Clinical Outcomes Study of Dysferlin-Deficient Limb–Girdle Muscular Dystrophy Type R2","authors":"Zoe White,&nbsp;Laura Rufibach,&nbsp;Heather Gordish Dressman,&nbsp;Heather Hilsden,&nbsp;Dan Cox,&nbsp;Simone Spuler,&nbsp;John W. Day,&nbsp;Kristi J. Jones,&nbsp;Diana X. Bharucha-Goebel,&nbsp;Emmanuelle Salort-Campana,&nbsp;Alan Pestronk,&nbsp;Maggie C. Walter,&nbsp;Carmen Paradas,&nbsp;Tanya Stojkovic,&nbsp;Madoka Mori-Yoshimura,&nbsp;Elena Bravver,&nbsp;Jordi Diaz-Manera,&nbsp;Elena Pegoraro,&nbsp;Jerry R. Mendell,&nbsp;the Jain COS Consortium,&nbsp;Volker Straub,&nbsp;Pascal Bernatchez","doi":"10.1002/jcsm.70042","DOIUrl":"https://doi.org/10.1002/jcsm.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Limb–girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, <i>DYSF</i>. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated cholesterol (HDL-C), non-HDL-C, creatine kinase (CK), transaminase levels and bilirubin were collected as part of the Jain Clinical Outcomes Study of Dysferlinopathy, a large multicentre LGMDR2 patient cohort (<i>N</i> = 188), along with ambulatory function values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We report that 43%, 49% and 50% of male patients were found to have abnormal circulating CHOL, HDL-C and non-HDL-C levels, respectively, whereas in female patients 39%, 37% and 30% of values were in the abnormal range. Overall, 68% of the total cohort had at least one abnormal cholesterol value (78% of males and 60% of females) and 89% of male CHOL/HDL-C ratios were in the suboptimal range (above 3.5). Although most patients were ambulant, the severity of circulating lipid abnormalities did not correlate with early loss of ambulation. Transaminase levels were lower in late-stage LGMDR2 samples, whereas bilirubin remained unchanged, suggesting a low muscular mass rather than hepatic origin and the absence of major liver damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Data from the largest natural history cohort of LGMDR2 patients support the concept that dyslipidemia is a comorbidity of LGMDR2, and the causal role of cholesterol abnormalities in muscle death should be further investigated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843752","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":"Biological Ageing Acceleration and Functional Capacities Across the Lifespan in the INSPIRE-T Cohort","authors":"Juan Luis Sánchez-Sánchez,&nbsp;Bruno Vellas,&nbsp;Sophie Guyonnet,&nbsp;Paul Bensadoun,&nbsp;Jean-Marc Lemaitre,&nbsp;Matias Fuentealba Valenzuela,&nbsp;Fabien Pillard,&nbsp;Yves Rolland,&nbsp;David Furman,&nbsp;Philipe de Souto Barreto","doi":"10.1002/jcsm.70046","DOIUrl":"https://doi.org/10.1002/jcsm.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Biological clocks are promising tools for the evaluation of biological age deviations (i.e., positive/negative acceleration). Here, we explored the associations of biological age acceleration (BAA) assessed by Horvath's, Hannum's, PhenoAge, and GrimAge epigenetic clocks, as well as the iAge inflammation-based clock, with functional capacities across adulthood and tested if chronological age and sex moderate these associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cross-sectional analysis was conducted with baseline (2019–2021) data from 1014 participants (age range 20–104 years old, 62.82% female) drawn from the Inspire Translational Human cohort, a community-based program in South-West France. Physical capacity endpoints included the five-time sit-to-stand test (5-STS), the Short Physical Performance Battery (SPPB), the 30-s chair stand test (30-s CST), maximum oxygen uptake (VO2max) and isokinetic muscle strength (IMS). Multivariate linear regression was used to explore the associations of BAA (with and without interacting with chronological age or sex) with functional capacity endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1014 individuals with available data on BAA and functional capacities were included (median age 64, IQR = 49–78, 62.82% female). GrimAge was the clock that more strongly correlated with functional capacities. Higher GrimAge BAA was associated with worse 5-STS (β = 0.25, 95% CI = 0.07, 0.43; <i>p</i> = 0.002), SPPB (β = −0.10, 95% CI = −0.18, −0.02; <i>p</i> = 0.019) and VO2max (β = −1.17, 95% CI = −1.81, −0.52; <i>p</i> &lt; 0.001) across the whole adulthood. When the moderation effect of age was explored, BAA acceleration assessed by GrimAge was associated with worse 30-s CST in early adulthood. Increased iAge BAA was associated with poor SPPB and 5-STS at older age, whereas Horvath's BAA correlated with a decline in 30-s CST.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among four DNA methylation epigenetic clocks and one inflammatory clock, our study shows that GrimAge is the biological ageing clock that best associates with different measures of functional capacity, from young to older adulthood.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843743","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":"The Predictive Power of the Cystatin C-Creatinine Score in Assessing Frailty","authors":"Li Deng,&nbsp;Xin Zheng,&nbsp;Yue Chen,&nbsp;Chenan Liu,&nbsp;Jinyu Shi,&nbsp;Zhaoting Bu,&nbsp;Xiaoyue Liu,&nbsp;Hong Zhao,&nbsp;Shuqun Li,&nbsp;Bing Yin,&nbsp;Siyu Xing,&nbsp;Hanping Shi","doi":"10.1002/jcsm.70040","DOIUrl":"https://doi.org/10.1002/jcsm.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As the global population ages, identifying reliable biomarkers to predict frailty and mortality is critical for early intervention. This study aims to construct a valuable biomarker and evaluate its predictive performance in assessing frailty and all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 3613 participants in the Health and Retirement Study (HRS) were used to construct the nomogram and main analysis, whereas data from the National Health and Nutrition Examination Survey were used to validate the robustness of the model. LASSO regression identified key biomarkers, and a nomogram was used to construct the score. The frailty index (FI) and all-cause mortality were used as the outcomes, and the score's predictive ability was evaluated using ROC curves, C-index and decision curve analysis. Subgroup analyses were conducted to assess the score's consistency across age, sex and clinical conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixteen haematological markers were selected through LASSO regression. The nomogram demonstrated that a scoring model based on cystatin C and creatinine can achieve optimal predictive performance. The Cystatin C-Creatinine Score demonstrated strong predictive power for frailty (AUC = 0.687) and all-cause mortality (AUC = 0.733). Logistic regression analysis showed a significant association between higher Cystatin C-Creatinine Scores and increased frailty risk, with participants in the high-risk group having an OR of 1.48 (95% CI: 1.35–1.62, <i>p</i> &lt; 0.001) compared to the low-risk group. Cox proportional hazards models also indicated that higher scores were associated with increased mortality risk (HR = 3.34, 95% CI: 1.75–6.38, <i>p</i> &lt; 0.001 for the high-risk group). In the validation set, the AUC values of the Cystatin C-Creatinine Score for predicting frailty and all-cause mortality reached 0.701 and 0.713, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings support the use of the Cystatin C-Creatinine Score as a practical and effective tool for identifying individuals at higher risk of frailty and mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853662","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":"Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A","authors":"Alexandre Pierre,&nbsp;Raphael Favory,&nbsp;Benoit Brassart,&nbsp;Claire Bourel,&nbsp;Raphael Romien,&nbsp;Sylvain Normandin,&nbsp;Arthur Dubech,&nbsp;Claire Vincent,&nbsp;Jeremy Lemaire,&nbsp;Gaelle Grolaux,&nbsp;Ophelie Not,&nbsp;Frederic Wallet,&nbsp;Frederic Daussin,&nbsp;Eric Boulanger,&nbsp;Arthur Durand,&nbsp;Marie Frimat,&nbsp;Alina Ghinet,&nbsp;Michael Howsam,&nbsp;William Laine,&nbsp;Philippe Marchetti,&nbsp;Jerome Kluza,&nbsp;Estelle Chatelain,&nbsp;Jimmy Vandel,&nbsp;Nicolas Barois,&nbsp;Valerie Montel,&nbsp;Bruno Bastide,&nbsp;Sebastien Preau,&nbsp;Steve Lancel","doi":"10.1002/jcsm.70041","DOIUrl":"https://doi.org/10.1002/jcsm.70041","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;Sepsis survivors often experience sustained muscle weakness, leading to physical disability, with no pharmacological treatments available. Despite these well-documented long-term clinical consequences, research exploring the cellular and molecular mechanisms is sorely lacking.&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;Bioinformatic analysis was performed in the &lt;i&gt;vastus lateralis&lt;/i&gt; transcriptome of human ICU survivors 7 days after ICU discharge (D7), 6 months (M6) and age- and sex-matched controls. Enrichment analysis using Gene Ontology (GO) terms and Mitocarta3.0 was performed at D7 and M6 on differentially expressed genes (DEGs) and modules identified by weighted gene co-expression network analysis (WGCNA). Using a murine model of resuscitated sepsis induced by caecal slurry injection, pathways identified by the bioinformatics analysis were explored in 18- to 24-week-old sepsis-surviving (SS) mice at Day 10. Autophagy flux was investigated both in vivo and in vitro with chloroquine, a lysosomal inhibitor and urolithin A (UA), an autophagy inducer. Systemic metabolism was evaluated with indirect calorimetry, muscle phenotype with in situ and ex vivo contractility, muscle mass, myofibre cross-sectional area and typing and mitochondrial population with transmission electron microscopy (TEM), as well as mitochondrial function with high-resolution respirometry. Autophagic vacuole (AV) level was monitored using LC3B-II and P62 protein expression and TEM.&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;Pathways related to ‘mitochondrion’ were the only ones whose deregulation persisted between D7 and M6 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and characterized WGCNA modules correlated with muscle mass, strength and physical function. Shared mitochondrial DEGs between D7 and M6 encoded matrix mitochondrial proteins related to ‘metabolism’ and ‘mitochondrial dynamics’. SS mice exhibited reduced complex I-driven oxygen consumption (CI-J&lt;sub&gt;O2&lt;/sub&gt;) (−45%), increased S-nitrosylation of complex I, damaged (+35%) and oxidized (+51%) mitochondria and AV accumulation (5 vs. 50 AVs/mm&lt;sup&gt;2&lt;/sup&gt;) compared with sham pair-fed mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) despite no differences in mitochondrial size or number. Autophagy flux was reduced in SS mice due to decreased AV degradation ratio (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). UA restored a balanced autophagy flux (turnover ratio 0.96 vs. −0.17) by increasing AVs formation and degradation ratio (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). UA also improved CI-J&lt;sub&gt;O2&lt;/sub&gt; (81 vs. 106 pmol/s/mg), tetanic force (215 vs. 244 mN/mm&lt;sup&gt;2&lt;/sup&gt;) and hindlimb muscle weight in SS mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853663","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":"Atrophy Masseter Recovery by Electrical Stimulation Mediated M2-Like Macrophage Polarisation via JAK/PI3K/AKT Pathway","authors":"Chuan Wu,&nbsp;Xiuyun Zheng,&nbsp;Qingchun Li,&nbsp;Yi Chen,&nbsp;Wei Liu,&nbsp;Xinyi Song,&nbsp;Quancheng Han,&nbsp;Qunyan Zhang,&nbsp;Chunfeng Fu,&nbsp;Qing Mei,&nbsp;Xiaoyu Liu,&nbsp;Junji Xu,&nbsp;Jian Zhou,&nbsp;Tingting Wu","doi":"10.1002/jcsm.70048","DOIUrl":"https://doi.org/10.1002/jcsm.70048","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;Atrophy of the masseter muscle can result in an aged facial appearance and diminished chewing function. Electrical stimulation (ES) is known for its ability to facilitate tissue healing and functional recovery, but its precise role in the repair of atrophic masseter muscles remains incompletely understood.&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 induced masseter muscle atrophy in rats through botulinum toxin (BTX) injection and subsequently treated the animals with or without ES. Single-nucleus sequencing (sn-RNA seq) was conducted to analyse the changes in macrophages of masseter muscles between control, BTX and BTX + ES groups. The role and mechanism of macrophage phenotypic transformation in the process of ES promoting the recovery of atrophied masseter muscles were both verified through in vivo and in vitro experiments.&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 results indicate that ES treatment within defined current parameters significantly ameliorated muscle condition by reducing atrophy-related gene expression (&lt;i&gt;MuRF1&lt;/i&gt;: BTX: 10.15 ± 1.69; BTX + ES: 1.05 ± 0.06; &lt;i&gt;Fbxo32&lt;/i&gt;: BTX: 8.62 ± 1.19, BTX + ES: 1.19 ± 0.07, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and enhancing vascularisation (Vegf positive area: BTX: 6.60 ± 2.87%, BTX + ES: 27.23 ± 1.70%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Analysis conducted with sn-RNA seq demonstrated increased infiltration of M1 macrophages during muscle atrophy, with a subsequent transition to M2 macrophages following ES treatment (M1 macrophage portion: Ctrl: 15.2%, BTX: 25.8%, BTX + ES: 14.7%; M2 macrophages: Ctrl: 67.9%, BTX: 46.9%, BTX + ES: 70.5%). Further investigations demonstrated that ES reduced M1 macrophage infiltration (five-fold lower of CD86&lt;sup&gt;+&lt;/sup&gt; cell number, BTX: 30 ± 2; BTX + ES: 6 ± 2, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) while increasing M2 macrophage presence (3.3-fold higher of CD163&lt;sup&gt;+&lt;/sup&gt;cell, BTX: 10 ± 3; BTX + ES: 33 ± 8, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), potentially via activation of the PI3K-Akt pathway (p-Akt/Akt ratio, BTX:0.58 ± 0.20%; BTX + ES:1.03 ± 0.07%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Depletion of macrophages using clodronate liposomes reversed the beneficial effects of ES on induced masseter atrophy (&lt;i&gt;MuRF1&lt;/i&gt;: BTX + ES: 2.20 ± 0.16; BTX + ES + CL: 12.93 ± 0.98, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), highlighting the involvement of macrophages in the therapeutic process. In vitro studies demonstrated that ES promoted the transition from M1 to M2 macrophages and enhanced proliferation and differentiation of myogenic cells.&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 findings ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853665","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}