Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Identification of Sarcopenic Obesity by Fat-to-Muscle Ratio in Older Adults: A Cohort Study","authors":"Daisuke Kakita,&nbsp;Kenji Harada,&nbsp;Satoshi Kurita,&nbsp;Masanori Morikawa,&nbsp;Chiharu Nishijima,&nbsp;Kazuya Fujii,&nbsp;Hiroyuki Shimada,&nbsp;Hidenori Arai","doi":"10.1002/jcsm.70174","DOIUrl":"10.1002/jcsm.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The diagnosis of sarcopenic obesity has been established in Europe and Japan, but screening tools remain inconsistent and lack standardization. The fat-to-muscle ratio (FMR) is a potential screening measure for sarcopenic obesity; however, its diagnostic accuracy compared with other tools has not been evaluated. This study compared the diagnostic performance of several screening tools for sarcopenic obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional analysis used data from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes (NCGG-SGS), a national cohort study conducted in Japan. In total, 7916 community-dwelling older adults (mean ± standard deviation age 73.5 ± 6.2 years, 54.8% females) were included. Sarcopenic obesity was diagnosed by the Japanese Working Group on Sarcopenic Obesity (JWGSO) criteria. The FMR and phase angle (PhA) were measured using the bioelectrical impedance analysis (BIA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Logistic regression analysis indicated that most screening tools, treated as continuous variables, were independently associated with sarcopenic obesity after adjustment for covariates; FMR (female: per 1-SD odds ratio [OR] = 3.06, 95% confidence interval [CI] = 2.53–3.71; male: OR = 3.09, 95% CI = 2.67–3.58), BMI (female: OR = 2.85, 95% CI = 2.35–3.58; male: OR = 1.43, 95% CI = 1.26–1.62), waist circumference (WC) (female: OR = 2.26, 95% CI = 1.86–2.74; male: OR = 1.24, 95% CI = 1.08–1.41) and PhA (female: OR = 1.12, 95% CI = 0.93–1.34; male: OR = 0.65, 95% CI = 0.56–0.76). Receiver operating characteristic (ROC) analysis showed moderate predictive ability for each screening tool: FMR (female: area under the curve [AUC] = 0.82, 95% CI = 0.79–0.85; male: AUC = 0.81, 95% CI = 0.79–0.84), BMI (female: AUC = 0.76, 95% CI = 0.72–0.79; male: AUC = 0.55, 95% CI = 0.51–0.59), WC (female: AUC = 0.70, 95% CI = 0.66–0.75; male: AUC = 0.53, 95% CI = 0.49–0.57) and PhA (female: AUC = 0.63, 95% CI = 0.58–0.69; male: AUC = 0.70, 95% CI = 0.67–0.74).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings suggest that the FMR is a more effective screening tool for identifying sarcopenic obesity than BMI, WC or PhA among community-dwelling older adults. Longitudinal studies are needed to confirm its predictive value across broader populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005214","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":"Pulmonary Obstruction and Age, Not Activity, Associate With Muscle Oxidative Impairment in Smokers With and Without COPD","authors":"Alessandra Adami,&nbsp;Fenghai Duan,&nbsp;Robert A. Calmelat,&nbsp;Zeyu Chen,&nbsp;Richard Casaburi,&nbsp;Harry B. Rossiter","doi":"10.1002/jcsm.70178","DOIUrl":"10.1002/jcsm.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low muscle oxidative capacity is an extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) with unclear aetiology. We sought to characterize locomotor muscle oxidative capacity in never smokers and ever smokers with and without COPD and determine clinical and behavioural features associated with low muscle oxidative capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two hundred forty-three adults enrolled in the <i>Muscle Health Study</i>, an observational study ancillary to COPDGene. G<i>astrocnemius</i> oxidative capacity was measured by near-infrared spectroscopy from the muscle oxygen consumption recovery rate constant (<i>k</i>). Physical activity was measured by accelerometry (vector magnitude units [VMU]/min). Pulmonary assessments included spirometry (FEV₁%predicted), diffusing capacity (DL_CO) and quantitative chest computed tomography (CT). Eighty-seven variables related to COPD features were considered. Variables selected by univariate analysis of log-transformed <i>k</i> with <i>p</i> ≤ 0.20 and filtered by machine learning were entered into multivariable linear regression to determine association with <i>k</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two hundred forty-one (53.1% female; 45.6% African American; 64 ± 10 years old) participants were allocated to analysis. FEV₁%predicted, DL_CO, CT, pack-years, age and VMU/min were among 24 variables selected by univariate analysis. After machine learning filtering on 162 (67%) cases with complete data, 11 variables were included in multivariable analysis. Only FEV₁%predicted, age and race were significantly associated with <i>k</i> (<i>R</i>² = 0.26). Model coefficients equate a 10% lower FEV₁%predicted to a 4.4% lower <i>k</i> or 10 years of aging to a 9.7% lower <i>k</i>. In 118 cases with CT available, FEV₁%predicted and age remained associated with <i>k</i> (<i>R</i>² = 0.24). Physical activity was not retained in any model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Physical activity or radiographic COPD manifestations were not significantly associated with muscle oxidative impairment. Across never smokers and ever smokers with and without COPD, locomotor muscle oxidative capacity was positively associated with FEV₁%predicted and negatively associated with age.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000844","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 Imaging in Inclusion Body Myositis: Refinement of MRI Criteria and Insights Into Upper Body Involvement","authors":"Eleonora Torchia,&nbsp;Matteo Lucchini,&nbsp;José Verdu-Diaz,&nbsp;Sara Bortolani,&nbsp;Beatrice Ravera,&nbsp;Vincenzo Carlomagno,&nbsp;Alessandra Cicia,&nbsp;Daniela Bernardo,&nbsp;Mauro Monforte,&nbsp;Robert Rehmann,&nbsp;Rudolf Andre Kley,&nbsp;Mario Sabatelli,&nbsp;Jordi Díaz-Manera,&nbsp;Enzo Ricci,&nbsp;Massimiliano Mirabella,&nbsp;Giorgio Tasca","doi":"10.1002/jcsm.70173","DOIUrl":"10.1002/jcsm.70173","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 diagnosis of inclusion body myositis (IBM) can be delayed because of its heterogeneous clinical presentation and the lack of specific biomarkers. Muscle imaging has gained increasing relevance over the past decade and is now included among the supportive criteria in the international diagnostic guidelines. This study aimed to refine MRI criteria for IBM to facilitate clearer pattern recognition, increase their reproducibility and broader clinical applicability. We also aimed to provide a comprehensive evaluation of muscle wasting across the entire body, including less frequently assessed regions such as the neck, scapular girdle and trunk muscles, and to explore the presence of radiological IBM phenotypes through cluster analysis.&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;Sixty-eight MRI scans and clinical records from patients diagnosed with IBM between 2003 and 2024 (60% males; mean age: 66 years, range: 46–85) were retrospectively reviewed. We defined a new set of three main and three supportive MRI criteria based on muscle imaging features and assessed their sensitivity. Whole body muscle involvement was semi-quantitatively scored using standardized scales across 6006 muscles. Pairwise correlation and K-means cluster analysis were performed to evaluate clinical–radiological relationships and identify phenotypic subgroups.&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 revised MRI criteria achieved 96% sensitivity. Performance was consistent across clinical subgroups and remained robust (83%) in patients with atypical onset. Whole-body analysis highlighted mild but frequent wasting of paraspinal (90% of scans) and neck and scapular girdle muscles (87%), while intracranial muscles were consistently unaffected. Correlation analysis underlined a significant association between radiological and functional involvement in the lower (&lt;i&gt;r&lt;/i&gt; = 0.57, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) but not in the upper body. Cluster analysis revealed two overlapping but distinguishable imaging phenotypes, characterized by different involvement of paraspinal and distal leg muscles. Cluster 1 showed a higher proportion of male patients.&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;The revised MRI criteria allow a reliable and easy recognition of the IBM pattern of muscle involvement, while whole-body imaging offers additional insights into disease heterogeneity and supports patient stratification in clinical trials. Clustering results also highlighted a possible sex-related influence on muscle vulnerability. The observed clini","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994800","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":"Association Between Abnormal DNA Methylation and Altered Transcriptome in Muscle Five Years After Critical Illness","authors":"Ceren Uzun Ayar,&nbsp;Fabian Güiza,&nbsp;Inge Derese,&nbsp;Greet Van den Berghe,&nbsp;Ilse Vanhorebeek","doi":"10.1002/jcsm.70170","DOIUrl":"10.1002/jcsm.70170","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;Critically ill patients requiring intensive care unit (ICU) admission suffer from muscle weakness that persists for years. Recently, altered RNA expression was documented in muscle of former ICU patients 5 years after critical illness that suggested disrupted mitochondrial function, disturbed lipid metabolism and fibrosis, of which many associated with the former patients' long-term loss of muscle strength. We hypothesized that abnormal DNA methylation detectable years after critical illness associates with these abnormal RNA expression patterns, as a potential biological basis for the persistent loss of muscle strength.&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;Genome-wide DNA methylation was assessed (Infiniumv2-HumanMethylationEPIC-BeadChips) in skeletal muscle biopsies from 118 former ICU patients harvested 5 years after critical illness (79.6% male, median 58 years, median BMI 27.3 kg/m&lt;sup&gt;2&lt;/sup&gt;) and 30 controls who never required ICU admission (76.7% male, median 61 years, median BMI 26.4 kg/m&lt;sup&gt;2&lt;/sup&gt;). Differentially methylated positions (DMPs) in former patients versus controls were identified, adjusting for age, sex, and BMI (minfi-package in R, Benjamini–Hochberg false-discovery-rate &lt; 0.05), followed by pathway over-representation of affected genes. Spearman correlations between DMP methylation and RNA expression were compared among groups of RNA with Z-test and Kolmogorov–Smirnov test. Risk factors for abnormal DNA methylation were identified with multivariable linear regression.&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;As compared with controls, former ICU patients showed 7379 DMPs (average difference 2.6% ranging up to 24.9%). They were associated with 1334 unique genes, enriched for muscle contraction, vascular development, cell differentiation and signal transduction. DMPs correlated more strongly with differentially expressed RNAs (DERNAs) than with non-differentially expressed RNAs (18.1% vs. 1.7% correlations with |rho| &gt; 0.3, &lt;i&gt;p&lt;/i&gt; &lt; 2.2 × 10&lt;sup&gt;−16&lt;/sup&gt;). Such correlations were more abundant among DERNAs associated with reduced muscle strength vs. those not associated (24.4% vs. 12.5%), also within the previously identified disrupted pathways (mitochondrial function 23.3% vs. 10.9%, lipid metabolism 15.9% vs. 7.2%, fibrosis 44.3% vs. 5.8%, all &lt;i&gt;p&lt;/i&gt; &lt; 2.2 × 10&lt;sup&gt;−16&lt;/sup&gt;). Older age, female sex, in-ICU treatment with glucocorticoids, benzodiazepines, early parenteral nutrition and opioids and insulin and antipsychotic medication at follow-up were most notably associated with more abnormal DNA methylation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994822","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":"Reference Methods for Measuring Skeletal Muscle Mass: A Critical Perspective","authors":"Steven B. Heymsfield,&nbsp;Houchun H. Hu,&nbsp;Edvin Johanssen,&nbsp;Sophia Ramirez,&nbsp;Gabriela de Oliveira Lemos,&nbsp;Maria Cristina Gonzalez,&nbsp;Carla M. Prado,&nbsp;Jonathan P. Bennett","doi":"10.1002/jcsm.70184","DOIUrl":"10.1002/jcsm.70184","url":null,"abstract":"<p>Skeletal muscle (SM) is an integral organ component in the pathophysiology of many acute and chronic diseases. But is there a ‘gold’ standard or accepted reference method for quantifying the amount and composition of human SM mass? Exploring that question led us to recognize the existence of a SM measurement paradigm that divides methods into two broad categories, in vitro and in vivo. In vitro methods quantify SM mass, weighing intact muscles as part of whole cadaver evaluations, only 51 of which are reported in medical literature with no recent additions. In vivo methods are used to evaluate SM in vivo, and two tiers were revealed in our analyses. An upper tier that included three methods considered ‘reference’ approaches for their accuracy and precision: computed tomography, magnetic resonance imaging and dual-energy X-ray absorptiometry. A lower in vivo method tier included bioimpedance analysis, three-dimensional imaging, several approaches involving creatine metabolism, ultrasound and anthropometry. A feature common to all of the lower tier methods is their need for calibration or validation against reference approaches in the upper in vivo method tier. A critical review of the three in vivo reference methods in the upper tier revealed widely variable SM volume/mass acquisition protocols, image analysis methods and applied terminology. Some reports espouse an upper tier reference method as the ‘gold’ standard while providing minimal details of exactly how and what was measured, thus making replication in follow-up studies difficult. Any technical issues related to an in vivo reference method are propagated to the in vivo methods in the lower tier that are calibrated or validated against them. Our review of in vivo reference methods of quantifying SM mass and composition led us to two broad recommendations. First, published reports including these reference methods should provide enough details related to acquisition and analysis protocols so that readers can replicate their findings. Second, an effort should be made to apply precise terminology in published reports in order to avoid confusion on exactly what was measured; suggestions are made on definitions of commonly used terms when referring to body composition compartments. Lastly, because there is no consensus on what constitutes a ‘gold’ standard for SM measurement, we suggest expert groups convene in the future to recommend optimum approaches and working guidelines for quantifying muscle mass and composition in vivo.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002799","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":"Distinct Metabolomic Alterations Are Associated With Physical Function, Weight Loss, and Muscle Mass in Men With Cancer","authors":"Lindsey J. Anderson,&nbsp;Lu Xia,&nbsp;Haiming Kerr,&nbsp;Marin Cabrera,&nbsp;Fabien Chu,&nbsp;Jaqueline Rose,&nbsp;Peter C. Wu,&nbsp;Atreya Dash,&nbsp;Sina A. Gharib,&nbsp;Jose M. Garcia","doi":"10.1002/jcsm.70183","DOIUrl":"10.1002/jcsm.70183","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;Treatments for cancer cachexia, defined as involuntary weight and muscle mass loss leading to significant functional impairment, remain unavailable partly due to insufficient improvement of clinically meaningful outcomes in current trials. By reflecting downstream effects of cellular function, metabolomics may identify mechanisms contributing to poor functional performance. Previous metabolomic studies in cancer cachexia have identified alterations in amino acid metabolism with weight loss or low muscularity; none have examined perturbations with poor physical function. We hypothesized that distinct metabolic signals in plasma and muscle are associated with weight loss, low muscle mass, and impaired function in cancer cachexia.&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 enrolled patients planning elective laparotomy for gastrointestinal or genitourinary cancer. Handgrip strength (HGS), stair climb power (SCP), and fasting plasma were collected within 2 weeks prior to surgery; rectus abdominis samples were obtained during surgery. Metabolomic perturbations associated with physical function (HGS, SCP), muscularity (lumbar cross-sectional area ‘CSA’ from opportunistic CT), or weight loss (&gt; 5% over previous 6 months) were examined in plasma and muscle. The Mann–Whitney U-test compared metabolite abundance between weight-losing and weight-stable patients, while Spearman's correlation tested associations of abundance with CSA, HGS, or SCP. The ‘Globaltest’ method assessed pathway alterations with weight loss, CSA, HGS, or SCP; the Benjamini-Hochberg adjustment was used to control for false discovery.&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;Patients (&lt;i&gt;N&lt;/i&gt; = 72) were male, median age 65 [interquartile range: 59–70], with 57% genitourinary cancer. Plasma and skeletal muscle metabolomic data were collected (&lt;i&gt;N&lt;/i&gt; = 64 and &lt;i&gt;N&lt;/i&gt; = 68, respectively). Weight loss was associated with significantly altered microbial, amino acid/derivative, fatty acid/lipid, and caffeine-related metabolism pathways in plasma (adjusted &lt;i&gt;p&lt;/i&gt; &lt; 0.1). Lower CSA was associated with significantly altered fatty acid/lipid, galactose, glycerophospholipid, and histidine metabolism and bile secretion pathways in skeletal muscle (adjusted &lt;i&gt;p&lt;/i&gt; &lt; 0.1). Worse HGS was nominally associated with altered plasma branched chain amino acid biosynthesis and altered skeletal muscle glutathione metabolism (unadjusted &lt;i&gt;p&lt;/i&gt; ≤ 0.05), while worse SCP was nominally associated with altered skeletal muscle amino sugar/nucleotide sugar metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis (unadjusted &lt;i&gt;p&lt;/i&gt; ≤ 0.0","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994799","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":"Integrated Proteomic and Metabolomic Profiling for Developing Novel Plasma-Based Diagnostic Models of Sarcopenia","authors":"Dongqin Xu,&nbsp;Haoran Jin,&nbsp;Jinlin Yang,&nbsp;Zhiliang Zuo,&nbsp;Rui Ou,&nbsp;Fengjuan Hu,&nbsp;Lu Pu,&nbsp;Yuxing Dong,&nbsp;Meng Wu,&nbsp;Birong Dong,&nbsp;Hao Jiang","doi":"10.1002/jcsm.70188","DOIUrl":"10.1002/jcsm.70188","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;Sarcopenia is a progressive, age-related condition characterized by a decline in skeletal muscle mass, strength and performance. Diagnosis remains challenging because current consensus criteria are difficult to scale and existing biomarkers lack accuracy. This study aimed to develop high-performance plasma-based diagnostic models for sarcopenia by integrating proteomic and metabolomic profiles.&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;Participants were selected from the West China Health and Aging Trend study. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Two independent 1:1 age- and sex-matched cohorts were constructed: a discovery cohort (40 sarcopenic, 40 non-sarcopenic) and a validation cohort (30 sarcopenic, 30 non-sarcopenic). Fasting plasma samples were profiled using the Olink Explore 384 Inflammation Panel and liquid chromatography–mass spectrometry-based untargeted metabolomics. Gaussian naïve Bayes classifiers were trained for single-omics models, and logistic regression was used to construct combined models in the discovery cohort and evaluate performance in the validation cohort.&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;Baseline age and sex were similar in sarcopenic and non-sarcopenic groups (discovery: median 72.0 vs. 71.5 years, &lt;i&gt;p&lt;/i&gt; = 0.714; validation: 71.0 vs. 71.5 years, &lt;i&gt;p&lt;/i&gt; = 0.594; women: 52.5% and 53.3%). The sarcopenic group had lower skeletal muscle index, grip strength and gait speed (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Sixty-five proteins and 268 metabolites differed between groups. A 7-protein Gaussian naïve Bayes model achieved AUCs of 0.743 (95% CI 0.718–0.767) in discovery and 0.698 (0.561–0.834) in validation; the metabolomic model yielded 0.828 (0.808–0.849) and 0.751 (0.617–0.885). Combined Model 1 integrated the probabilistic outputs of the proteomic (7 proteins) and metabolomic (7 metabolites) models and reached AUCs of 0.951 (0.937–0.965) and 0.823 (0.717–0.930), outperforming single-omics models (discovery: both &lt;i&gt;p&lt;/i&gt; &lt; 0.001; validation: vs. proteomic &lt;i&gt;p&lt;/i&gt; &lt; 0.05; vs. metabolomic &lt;i&gt;p&lt;/i&gt; = 0.147). Combined Model 2 incorporated only the top two biomarkers from each platform (CCL13, FGF2, N-hexadecanoylpyrrolidine and 1-(cyclohexylmethyl)proline), achieving AUCs of 0.853 (0.828–0.878) in discovery and 0.911 (0.839–0.983) in validation and remained superior to single-omics models (discovery: both &lt;i&gt;p&lt;/i&gt; &lt; 0.001; validation: both &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Its validation performance was comparable to Combined Model 1 (&lt;i&gt;p&lt;/i&gt; = 0.124), with sensitivity 86.7%, specificity 80.0%, precision 81.2% and F1-sc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986439","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 Transporter ABCB10 Protects Against Doxorubicin-Induced Respiratory Muscle Dysfunction Independent of Changes to Diaphragm Accumulation","authors":"Ashley J. Smuder,&nbsp;Vivian Doerr,&nbsp;Cesar E. Jacintho Moritz,&nbsp;Jie Li,&nbsp;Branden L. Nguyen","doi":"10.1002/jcsm.70171","DOIUrl":"10.1002/jcsm.70171","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;Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose use can cause respiratory toxicity, increasing patient fatigue and negatively impacting quality of life and survival. These adverse effects occur due to diaphragm muscle mitochondrial accumulation of DOX, where it causes reactive oxygen species production and iron dysregulation. ABCB10 is a mitochondria-localized ATP-binding cassette transporter hypothesized to play a role in the maintenance of mitochondrial redox balance and iron homeostasis, and potentially the mitochondrial export of DOX. This study investigated potential therapeutic effects of ABCB10 to prevent DOX-induced respiratory muscle dysfunction.&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;DOX respiratory muscle toxicity was modelled in rats using both single (20 mg/kg, once) and multicycle (5.7 mg/kg, 3 cycles) administration. The effects of overexpression and knockdown of ABCB10 on DOX-induced diaphragm dysfunction, mitochondrial DOX accumulation and markers of mitochondrial iron homeostasis were evaluated via administration of rAAV9-MHCK7-ABCB10 or an antisense oligonucleotide targeting ABCB10, 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;ABCB10 significantly improved diaphragm rate of fatigue (138.2 ± 11.66 s vs. 104.6 ± 8.79 s in DOX), specific force production (22.12 ± 0.70 N/cm&lt;sup&gt;2&lt;/sup&gt; vs. 18.31 ± 1.65 N/cm&lt;sup&gt;2&lt;/sup&gt; at 160 Hz in DOX) and fibre area (Type I: 1309.05 ± 56.86 μm&lt;sup&gt;2&lt;/sup&gt; vs. 1027.04 ± 50.53 μm&lt;sup&gt;2&lt;/sup&gt; in DOX; Type IIa: 1389.13 ± 47.72 μm&lt;sup&gt;2&lt;/sup&gt; vs. 1027.04 ± 50.07 μm&lt;sup&gt;2&lt;/sup&gt; in DOX; Type IIb/x: 2590.81 ± 103.21 μm&lt;sup&gt;2&lt;/sup&gt; vs. 2302.13 ± 138.62 μm&lt;sup&gt;2&lt;/sup&gt; in DOX) following a single injection of DOX. These improvements did not occur as a result of ABCB10-induced efflux of DOX (1006.03 ± 214.30 pg/μg vs. 1008.69 ± 195.62 pg/μg in DOX) but were associated with reduced mitochondrial iron (0.17 ± 0.02 nmol/mg vs. 0.23 ± 0.02 nmol/mg in DOX). The beneficial effects on diaphragm rate of fatigue (136.5 ± 11.93 s vs. 121.5 ± 9.47 s in DOX), specific force production (23.36 ± 1.40 N/cm&lt;sup&gt;2&lt;/sup&gt; vs. 19.26 ± 1.21 N/cm&lt;sup&gt;2&lt;/sup&gt; at 160 Hz in DOX) and fibre area (Type I: 1124.68 ± 63.02 μm&lt;sup&gt;2&lt;/sup&gt; vs. 914.57 ± 63.09 μm&lt;sup&gt;2&lt;/sup&gt; in DOX; Type IIa: 1244.67 ± 106.18 μm&lt;sup&gt;2&lt;/sup&gt; vs. 950.02 ± 62.38 μm&lt;sup&gt;2&lt;/sup&gt; in DOX; Type IIb/x: 2548.37 ± 235.69 μm&lt;sup&gt;2&lt;/sup&gt; vs. 2222.17 ± 234.61 μm&lt;sup&gt;2&lt;/sup&gt; in DOX) were also present in rats that received multiple cycles of DOX. Diaphragm rescue with ABCB10 was attendant with reduced mitoferrin 1 gene expression (+1.62 ± 0.47 fold vs. +3.85 ± 0.99 fold in DOX), preservation of ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986399","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 Mass Modifies the Prognostic Impact of LDL Cholesterol in Chronic Heart Failure","authors":"Ryosuke Sato,&nbsp;Tania Garfias-Veitl,&nbsp;Guglielmo Fibbi,&nbsp;Mirela Vatic,&nbsp;Wolfram Doehner,&nbsp;Stefan D. Anker,&nbsp;Stephan von Haehling","doi":"10.1002/jcsm.70168","DOIUrl":"10.1002/jcsm.70168","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;Dyslipidaemia is among the major risk factors for atherosclerotic cardiovascular disease. Paradoxically, higher cholesterol levels are associated with better survival in heart failure (HF) of any aetiology. Because cholesterol is an integral component of skeletal muscle structure, one possible explanation involves the interplay between lipid metabolism and skeletal muscle health. Using data from the Studies Investigating Comorbidities Aggravating Heart Failure, we investigated whether an association exists between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in patients with chronic HF in the context of skeletal muscle mass.&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 241 patients with chronic HF (68 ± 11 years, 80% male, left ventricular ejection fraction 39% ± 13%) were enrolled. LDL-C levels were divided into low and high based on the median value (93 mg/dL). The appendicular skeletal muscle mass index (ASMI) was assessed using a dual-energy X-ray absorptiometry scan and divided into high and low based on the sex-specific median value (men = 7.97 kg/m&lt;sup&gt;2&lt;/sup&gt;, women = 6.87 kg/m&lt;sup&gt;2&lt;/sup&gt;). Patients were divided into four groups based on median LDL-C levels and ASMI values.&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;During a median follow-up of 6.3 years, 95 patients (39%) died. There were differences in mortality between the four groups, with the highest mortality in patients with low LDL-C levels and low ASMI and the lowest mortality in patients with high LDL-C levels and high ASMI (&lt;i&gt;p&lt;/i&gt; = 0.002, by log-rank). The low LDL-C group had higher mortality compared with the high LDL-C group (46% vs. 33%, &lt;i&gt;p&lt;/i&gt; = 0.01, by log-rank). Multivariate Cox proportional hazard analysis confirmed the association between the low LDL-C group and higher mortality (adjusted hazard ratio [aHR] 1.65 [1.00–2.72], &lt;i&gt;p&lt;/i&gt; = 0.04). This prognostic impact of low LDL-C appeared greater in the low ASMI group than in the high ASMI group (56% vs. 37%, &lt;i&gt;p&lt;/i&gt; = 0.01, and 36% vs. 28%, &lt;i&gt;p&lt;/i&gt; = 0.28, by log-rank: &lt;i&gt;p&lt;/i&gt; for interaction = 0.47). In the low ASMI group, lower LDL-C levels were predictors of mortality in multivariate Cox proportional hazard models (aHR 1.46–1.48 per 1 SD decrease in LDL-C, all &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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;In patients with chronic HF, lower LDL-C levels were associated with higher mortality, especially in the low ASMI group. These findings suggest that low cholesterol levels may exacerbate skeletal musc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972250","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":"Current Trends in Duchenne Muscular Dystrophy Research and Therapy: 3D Cardiac Modelling","authors":"Marta Przymuszała,&nbsp;Marta Białobrzeska,&nbsp;Józef Dulak,&nbsp;Urszula Florczyk-Soluch","doi":"10.1002/jcsm.70180","DOIUrl":"10.1002/jcsm.70180","url":null,"abstract":"<p>Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, presents a multifaceted challenge that affects both skeletal muscle function and cardiomyocyte homeostasis, causing progressive degeneration and life-threatening cardiac complications by adolescence. Current treatments fail to prevent poor prognoses, and while FDA-approved therapies show promise in targeting dystrophin restoration, including RNA-based approaches and microdystrophin gene therapy, clinical evidence supporting their efficacy remains limited. Substantial challenges persist, particularly in achieving effective cardiac targeting, ensuring long-term safety and developing scalable treatments. Alternative therapies addressing muscle and cardiac pathophysiology are being explored alongside dystrophin-based approaches. DMD treatment is increasingly focusing on heart targeting with optimized cardiac-specific delivery strategies. Human-induced pluripotent stem cells (hiPSCs) enable DMD modelling, bridging pathophysiology and clinical phenotypes. DMD patient–specific hiPSC-derived cardiomyocytes (hiPSC-CMs) serve as in vitro models for disease mechanisms and therapy, with 3D cardiac models, either self-organizing (spheroids) or moulded, expanding on hiPSC-CMs to reflect cell interactions and myocardial tissue architecture. Advanced methods like 2D cell sheets, patches and engineered 3D human cardiac models show potential for improving cell engraftment and functional recovery in injured hearts, but their direct therapeutic application in DMD remains speculative due to extensive muscle mass loss; the complexity of cardiac and skeletal muscle interactions; and unresolved challenges related to cell integration, maturation and long-term function. Considering the premature state of cell-based therapies in this complex disease, current DMD treatment efforts focus on genetic approaches. Progress will likely depend on combining dystrophin-restoring strategies with therapies targeting disease mechanisms and improving cardiac delivery.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"17 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907718","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}