Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Cancer IDO1-Mediated Tryptophan-Kynurenine Metabolic Reprogramming to Drive Skeletal Muscle Atrophy and Cachexia Acceleration.","authors":"Leng Han,Lingjie Jing,Xinting Zhu,Ciqin Li,Lu Bai,Yang Fang,Yuxuan Zhou,Dingyuan Bai,Jin Lu,Yonglong Han,Cheng Guo,Shumin Zhou,Quanjun Yang","doi":"10.1002/jcsm.70295","DOIUrl":"https://doi.org/10.1002/jcsm.70295","url":null,"abstract":"BACKGROUNDCancer cachexia is a debilitating syndrome characterized by severe skeletal muscle wasting, which significantly impairs patient quality of life and survival. Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme in tryptophan (Trp) metabolism, is often upregulated in cancers, but its specific role in driving lung cancer-associated cachexia remains inadequately defined. This study investigated the mechanistic role of Ido1 in cancer cachexia and evaluated the therapeutic potential of its inhibition.METHODSWe established Lewis lung carcinoma (LLC) models in C57BL/6 mice using wild-type, Ido1-overexpressing (Ido1-OE) and Ido1-knockout (Ido1-KO) cells. Muscle mass, tumour growth and metabolic changes were assessed in vivo. Transcriptomic and targeted metabolomic analyses were performed on muscle and serum samples. In vitro, we examined the effects of tumour-conditioned media, the Trp metabolite kynurenine (Kyn) and Trp supplementation on C2C12 myotube atrophy. In vivo experiments verified the efficacy of the Ido1 inhibitor palmatine hydrochloride (PAL). Molecular pathways were analysed via western blot and qPCR.RESULTSCompared to LLC mouse models, Ido1-OE significantly exacerbated tumour growth and cachexia, leading to a significant decrease in lean body weight, gastrocnemius and tibialis anterior muscle weights (p < 0.01, p < 0.0001, p < 0.001). Gastrocnemius muscle fibre cross-sectional area significantly decreased in the Ido1-OE group (p < 0.0001). Transcriptomic analysis revealed that Ido1-OE activated pro-inflammatory and protein degradation pathways (upregulating MuRF1/Atrogin1, p < 0.05) while suppressing anabolic signalling pathways (oestrogen pathways, p < 0.01). Metabolomics analysis revealed unique metabolic signatures in Ido1-OE mice: Trp depletion and Kyn accumulation. In vitro experiments demonstrated that Ido1-OE enhanced LLC cell proliferation and migration capabilities (p < 0.0001, p < 0.0001). Tumour-conditioned medium (TCM) derived from Ido1-OE tumours significantly induced C2C12 myotube atrophy (p < 0.01). Similarly, direct treatment with Kyn led to dose-dependent muscle fibre shrinkage, with significant atrophy observed at 30 μM (p < 0.01) and 100 μM (p < 0.0001). Notably, the myotube atrophy induced by Kyn was significantly reversed by the addition of supplemental Trp (p < 0.0001). Compared with the Ido1-OE group, PAL treatment reduced gastrocnemius and tibialis anterior atrophy (p < 0.01; p < 0.05). Mechanistically, PAL inhibited the mRNA expression levels of MuRF1/Atrogin1 (p < 0.0001, p < 0.001), as well as their corresponding protein levels (p < 0.0001, p < 0.0001). Furthermore, PAL restored the phosphorylation level of mTOR (p < 0.001), as well as the mRNA expression of myosin heavy chain (p < 0.01).CONCLUSIONSOur findings demonstrate that Ido1 accelerates muscle atrophy and cancer cachexia by driving a metabolic reprogramming centred on the Trp-Kyn pathway. Pharmacological inhibition of Ido1 with PAL effectively miti","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"21 1","pages":"e70295"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not All Weight Loss Is Equal: Towards Muscle-Preserving Therapies in Obesity.","authors":"Joseph D Abraham,Muhammad Shahzeb Khan,Stefan D Anker","doi":"10.1002/jcsm.70298","DOIUrl":"https://doi.org/10.1002/jcsm.70298","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"4 1","pages":"e70298"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota-Linked Benefits of Low-Intensity Pulsed Ultrasound Rejuvenate the Ageing Muscle.","authors":"Jia-Hua Jhuang,Kuo-Cheng Lan,Ting-Yu Chang,Ding-Cheng Chan,Shing-Hwa Liu","doi":"10.1002/jcsm.70291","DOIUrl":"https://doi.org/10.1002/jcsm.70291","url":null,"abstract":"BACKGROUNDAgeing is an inevitable biological process that contributes to increased prevalence of age-associated diseases, including sarcopenia, defined by progressive loss of muscle mass, functional decline and a heightened risk of injury. Developing effective interventions remains a critical clinical priority. This study employed a natural ageing mouse model to investigate whether noninvasive low-intensity pulsed ultrasound (LIPUS), a therapeutic ultrasound, delivered to the abdomen, could alleviate age-related muscle deterioration and whether its effects were linked to gut microbiota modulation.METHODSC57BL/6 mice were maintained until 92 weeks of age, after which abdominal LIPUS stimulation was administered for 8 weeks. At 100 weeks, both forelimb and hind limb grip strength were assessed prior to euthanasia. Faecal samples from the distal colon were collected for microbiota profiling, and gastrocnemius muscles were harvested for downstream analyses.RESULTSNaturally aged mice exhibited sarcopenia-like characteristics, including impaired muscle performance, reduced myofiber diameter and decreased muscle weight (n = 6, p < 0.01, p < 0.001). Age-related renal impairment promoted the accumulation of advanced glycation end products (AGEs) in skeletal muscle, triggering pro-inflammatory signalling cascades characterized by elevated COX-2, phosphorylated NF-κB, NLRP3, IL-1β and Caspase-1 (n = 5-6, p < 0.01). LIPUS treatment significantly improved muscle strength (forelimb and hind limb grip strength, n = 6, p < 0.001, p < 0.01) and muscle mass (n = 6, p < 0.01), while suppressing inflammatory mediators (n = 5-6, p < 0.05). Gut microbiota analysis showed that LIPUS increased microbial diversity (n = 5-6, p < 0.05) and altered taxonomic composition, enriching anti-inflammatory taxa such as Lactobacillus, Bifidobacterium, Faecalibaculum and Coriobacteriaceae_UCG_002 (n = 6, p < 0.05). Correlation analysis indicated that these LIPUS-enriched taxa were positively associated with enhanced muscle performance. These data suggest that LIPUS mitigates sarcopenia in naturally aged mice by restoring muscle integrity and attenuating inflammation, possibly via gut microbiota regulation.CONCLUSIONSThis study shows that natural ageing in mice induces sarcopenia-like features with inflammatory activation and gut microbiota alterations. Abdominal LIPUS treatment alleviated muscle loss, reduced inflammation and promoted beneficial microbes, rejuvenating the ageing muscle. These findings highlight LIPUS as a safe, noninvasive and potentially translatable strategy for sarcopenia, warranting further investigation of its microbiota-muscle interactions.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"73 1","pages":"e70291"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinase YOD1 Inhibition Suppresses DEX- and Denervation-Induced Muscle Atrophy Through MAFbx Destabilization.","authors":"Jongbeom Chae,Seon Min Woo,Seung Un Seo,Simmyung Yook,Hyo Je Cho,Jung Yeol Lee,Kyoung Jin Min,Junhyeon Park,Dongryeol Ryu,Taeg Kyu Kwon","doi":"10.1002/jcsm.70300","DOIUrl":"https://doi.org/10.1002/jcsm.70300","url":null,"abstract":"BACKGROUNDSMuscle atrophy, characterized by progressive loss of muscle mass and function, is driven by muscle-specific E3 ligases MAFbx and MuRF1. While transcriptional regulation of E3 ligases is documented, the mechanism of their regulation by the ubiquitin-proteasome system remains unclear. This study aims to identify a deubiquitinase (DUB) regulating these E3 ligases and reveal the mechanisms underlying the mitigation of muscle atrophy through inhibition of the discovered DUB.METHODSDifferentiated C2C12 myotubes were screened using siRNAs to identify DUB genes that can regulate muscle atrophy. Muscle fibre cross-sectional area (CSA), grip strength and gene expression (MAFbx, MyoD, etc.) were evaluated in muscle atrophy-induced mouse model. Human translational relevance was analysed using GTEx skeletal muscle data.RESULTSWe identified that OTU DUBs family genes are increased (log2 FC > 1, p < 0.05) in DEX-induced muscle atrophy. Pharmacological (ubiquitin isopeptidase inhibitor I, G5) and genetic inhibition of YOD1 alleviated DEX- and denervation-induced muscle atrophy by MAFbx destabilization. The UBX domain of YOD1 was found to interact with the LZ domain of MAFbx, and YOD1 stabilized the MAFbx protein by removing polyubiquitin chains at lysine 48 in MAFbx. In in vivo mouse models, G5 treatment effectively ameliorated DEX- or NTX-induced muscle atrophy. Specifically, G5 increased grip strength by 37.64% (DEX, p < 0.0001) and 36.37% (NTX, p < 0.01), while muscle fibre size was improved by 35.85% (DEX, p < 0.01) and 30.76% (NTX, p < 0.0001). These improvements were accompanied by the restoration of MyoD and eIF3-f expression. Consistently, GTEx-based analysis revealed that high YOD1 expression in human skeletal muscles is significantly associated with an increased proportion of smaller fibres (< 2000 μm2), correlating with enriched proteostasis (NES = 1.51)-related and muscle development (NES = -1.44)-related transcriptional signatures.CONCLUSIONSOur study indicates that YOD1 inhibition destabilizes MAFbx protein levels, leading to protection against DEX- and denervation-induced muscle atrophy. Integration of human GTEx data further supports the translational relevance of YOD1 as a regulator of muscle fibre homeostasis. This study provides new insights into the post-translational regulation of muscle-specific E3 ligases and presents evidence showing that targeting YOD1 is a promising therapeutic approach for the prevention and treatment of muscle atrophy.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"6 1","pages":"e70300"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Study of Frailty Phenotype in Relation to Chronic Kidney Disease Incidence.","authors":"Yong-Xiang Ruan,Da-Chuan Guo,Wen-Hao Liu,Jia-Man Ou,Qi Guo,Jing-Wei Gao,Yang-Wei Cai,Mao-Xiong Wu,Xiao-Tian Liang,Jie-Wen Cai,Pin-Ming Liu,Jing-Feng Wang,Hai-Feng Zhang,Yang-Xin Chen","doi":"10.1002/jcsm.70287","DOIUrl":"https://doi.org/10.1002/jcsm.70287","url":null,"abstract":"BACKGROUNDThe longitudinal relationship between frailty phenotype and CKD development, and the modifying role of genetic CKD risk in this association, remains unclear. Research on simple, noninvasive and quantifiable CKD prediction models incorporating frailty is limited.METHODSWe analysed 214 502 CKD-free participants from the UK Biobank cohort. Frailty was assessed using a modified phenotype with five components: weight loss, exhaustion, low grip strength, low physical activity and slow gait speed, to match UK Biobank data. Self-reported walking pace and weight change served as proxies where objective measures were unavailable. A polygenic risk score for CKD was calculated based on 258 single nucleotide polymorphisms. Cox proportional hazards models were used to assess the association between the frailty phenotype and new-onset CKD. The interaction between frailty and genetic risk on CKD outcomes was also examined. A noninvasive CKD prediction model, integrating frailty, age, gender, diabetes, hypertension, BMI and smoking status, was developed and validated internally using the UK Biobank and externally using CHARLS cohorts.RESULTSAmong the 214 502 CKD-free participants with a median age of 57 (49-62) years, 50.3% were female. A total of 109 290 individuals (51.0%) were classified as non-frail, 96 941 (45.2%) as pre-frail and 8271 (3.9%) as frail. Over the course of a median follow-up period of 12.9 years, we documented 8079 (3.8%) cases of CKD. Compared with non-frailty, the hazard ratio (HR) for new-onset CKD in prefrailty and frailty was 1.143 (95% CI, 1.090-1.199, p < 0.001) and 1.606 (95% CI, 1.474-1.749, p < 0.001) in the multivariate model, respectively. Each one-point increase in frailty score was associated with a higher risk of CKD (HR = 1.142; 95% CI, 1.116-1.170, p < 0.001) in the multivariable model. Participants with frailty and high genetic risk had the greatest risk of CKD (HR = 1.981; 95% CI, 1.733-2.266, p < 0.001) compared with those without frailty and low genetic risk. In the simple CKD prediction model incorporating frailty, it demonstrated an AUC of 0.734 at 5 years, 0.745 at 8 years and 0.749 at 10 years in internal testing. External validation also showed consistent discrimination and calibration with an AUC of 0.740.CONCLUSIONSPre-frail and frail phenotypes were associated with a higher risk of developing CKD, showing a dose-response relationship. A noninvasive prediction model incorporating frailty and clinical parameters exhibited stable discriminative performance over a decade in both European and Asian cohorts.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"6 1","pages":"e70287"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Tissue and Lipid Dysregulation Contributions to Cachexia, Sarcopenia and Muscle Function.","authors":"Joseph D Abraham,Stephan von Haehling,Stefan D Anker","doi":"10.1002/jcsm.70299","DOIUrl":"https://doi.org/10.1002/jcsm.70299","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"13 1","pages":"e70299"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Drivers and Molecular Mechanisms of Sarcopenia in Aetiology-Specific End-Stage Liver Disease.","authors":"Thomas Nicholson,Sophie L Allen,Jonathan I Quinlan,Amritpal Dhaliwal,Michael Macleod,Joshua Price,Jon Hazeldine,Michael S Sagmeister,Caitlin Ditchfield,Kirsty C McGee,Felicity R Williams,Ahmed M Elsharkawy,Matthew J Armstrong,Carolyn A Greig,Janet M Lord,Leigh Breen,Simon W Jones","doi":"10.1002/jcsm.70294","DOIUrl":"https://doi.org/10.1002/jcsm.70294","url":null,"abstract":"BACKGROUNDPatients with end-stage liver disease (ESLD) often present with sarcopenia, defined as loss of skeletal muscle mass and quality, which is associated with reduced quality of life and increased mortality. However, the molecular mechanisms driving sarcopenia in ESLD are not fully understood and there are currently no therapeutic interventions. This study aimed to identify potential circulating factors contributing to sarcopenia progression in ESLD by assessing their role in driving transcriptomic alterations in skeletal muscle.METHODSQuadriceps muscle tissue, plasma and serum were obtained from ESLD patients (n = 24) and age/sex-matched healthy controls (HC; n = 18) (Clinical Trial ID: NCT04734496, Ethical Approval 18/WM/0167). Total RNA from snap-frozen vastus lateralis muscle biopsies underwent RNA sequencing (Illumina). Serum concentrations of 60 cytokines were profiled by Luminex and ELISA, with comparisons made both between ESLD and HC, and across ESLD aetiologies (alcohol-related, NAFLD, viral hepatitis, other). In vitro, primary human myotubes (from non-ESLD aged donors, NRES #16/SS/0172) were treated with 10% ESLD or HC plasma (24 h, n = 6 per group) followed by RNA sequencing (BGI Genomics). Differentially expressed genes (p < 0.05, fold-change > 1.5) were identified via Qlucore and DESeq2, and pathway analysis performed using Ingenuity (Qiagen). The impact of physiological concentrations of candidate cytokines (IL-1α, GDF-15 and HGF) on myotube thickness, differentiation and mitochondrial function was assessed by immunofluorescence microscopy, RT-qPCR and metabolic flux assays.RESULTSIn ESLD muscle, 387 and 225 genes were significantly up- and downregulated compared to HC, respectively, with cellular senescence identified as a top dysregulated function. Upstream regulator analysis predicted activation of hepatocyte growth factor (HGF) and interleukin-1 signalling. Subgroup analysis revealed distinct transcriptomic profiles based on disease aetiology. Serum profiling identified 15 cytokines significantly elevated (p < 0.05) and five reduced (p < 0.05) in ESLD, including increased HGF and reduced interleukin-1 receptor antagonist. Stratified analysis also revealed aetiology specific cytokine profiles, with only GDF-15 significantly (p < 0.0001) elevated in all groupsTwenty-four-hour ESLD plasma treatment induced 423 differentially expressed genes in human myotubes, which were again associated with significant activation of senescence pathways, with IL-1 identified as a key upstream driver. In vitro, IL-1α, GDF-15, and HGF significantly reduced myotube thickness, nuclear fusion index and perturbed metabolism (increased glycolysis, impaired oxidative phosphorylation).CONCLUSIONSCollectively, these findings suggest that sarcopenia in ESLD is driven by aetiology-specific mechanisms, highlighting the potential for targeted therapies to improve muscle mass and function.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"250 1","pages":"e70294"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole Genome Sequence Analysis of Weight Loss in 16 972 Participants With COPD Reveals Novel Risk Loci in DRAIC and RFX3.","authors":"Joe W Chiles,Alison Rocco,Vinodh Srinivasasainagendra,Harry B Rossiter,Richard Casaburi,Anna Thalacker-Mercer,J Michael Wells,Emily S Wan,Edwin K Silverman,Michael H Cho,Craig P Hersh,Bruce M Psaty,Sina A Gharib,Yan Gao,George T O'Connor,Leslie A Lange,Stephen S Rich,Ani W Manichaikul,R Graham Barr,Victor E Ortega,Deborah A Meyers,Albert V Smith,Hemant K Tiwari,Merry-Lynn N McDonald","doi":"10.1002/jcsm.70293","DOIUrl":"https://doi.org/10.1002/jcsm.70293","url":null,"abstract":"BACKGROUNDChronic obstructive pulmonary disease (COPD) is associated with musculoskeletal comorbidities, including cachexia. Weight loss (WL) is the major criterion for cachexia and increases risk for mortality in COPD. Risk factors for WL in COPD are incompletely understood. We performed this whole genome sequencing (WGS) analysis to identify genetic risk variants for WL in COPD.METHODSWe studied 16 972 participants from the Trans-Omics for Precision Medicine (TOPMed) Initiative and All of Us Research Program. COPD was diagnosed using spirometry in TOPMed, while diagnosis codes were used in All of Us. WL was defined as WL ≥ 5% or a final body mass index (BMI) &lt; 20 kg/m2. WGS data came from white blood cells in all cohorts. Single-variant testing was conducted on both race- and study-stratified cohorts and in a cosmopolitan, ancestry-independent manner using GENESIS in TOPMed and SAIGE in All of Us. SAIGE-GENE+ gene-based analyses were performed on race-stratified and cosmopolitan cohorts. Single variant meta-analyses were conducted using METAL within (B/AA and NHW analyses of Black/African-American and non-Hispanic white participants, respectively) and across racial groups (COSMO). Rare variant gene-based results were combined using Fisher's method. Transcriptomic effects were predicted using MetaXcan. We used the GWAS Catalogue to analyse for colocalization with other related traits.RESULTSTwo single variants were associated with WL in COPD among All of Us participants: one intronic variant in HCN1 in Black/African-American participants (chr5:45271359:TACACAC:T, odds ratio with 95% confidence interval (OR (CI95)) = 2.43(1.78-3.31), p = 1.95 × 10-8) and one intergenic variant between PPP4R2 and PDZRN3 in the cosmopolitan and NHW cohorts (chr3:73345901:A:G, OR (CI95) = 0.21(0.12-0.35), p = 8.84 × 10-9 in cosmopolitan and OR (CI95) = 0.18(0.10-0.33), p = 9.44 × 10-9 in NHW). Single-variant meta-analysis identified two loci associated with WL in COPD: five variants within DRAIC in the B/AA meta-analysis (lead variant chr15:69571341:A:G, OR (CI95) = 1.37(1.23-1.51), p = 1.29 × 10-9) and two intronic variants within RFX3 in the cosmopolitan meta-analysis (lead variant chr9:3390983:T:C, OR (CI95) = 1.50(1.31-1.73), p = 1.06 × 10-8). Rare variants within RNU6-565P (NHW analysis in All of Us; p = 2.83 × 10-7) and LOC339298 (B/AA analysis in All of Us, p = 1.85 × 10-6) were associated with WL in COPD. The RNU-565P signal remained significant after combination with TOPMed results (pcombined = 1.23 × 10-6). MetaXcan predicted differential expression of LNC00959 in visceral adipose tissue (p = 1.16 × 10-6 in COSMO analysis). Colocalization analyses identified genomic associations between BMI and variants in or near DRAIC, RFX3, PDZRN3, and LINC00959.CONCLUSIONSIn the first WGS analysis of WL in COPD, we have identified seven novel loci. Further characterization of these loci will validate our findings and improve our understanding of the molecular pathophys","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"25 1","pages":"e70293"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Body Composition and Physical Function With Incident Diabetes in Older Adults: A 14‐Year Prospective Cohort Study","authors":"Ting Zhang, Shuyi Li, Yafei Wu, Jason Leung, Alice Pik‐Shan Kong, Amany K. Elshorbagy, T. W. Auyeung, Timothy Kwok","doi":"10.1002/jcsm.70297","DOIUrl":"https://doi.org/10.1002/jcsm.70297","url":null,"abstract":"Background Longitudinal associations between age‐related changes in body composition, physical performance and incident diabetes mellitus (DM) in older adults and the mediating role of branched‐chain amino acids (BCAAs) remain understudied. Methods This prospective cohort study included 4000 community‐dwelling older adults at baseline. Longitudinal analysis of incident DM involved 3421 participants without baseline DM. Incident DM was identified through self‐reported diagnosis, medication use, hospital records or fasting glucose ≥ 7.0 mmol/L. Body composition (PBF [percent body fat], FMI [fat mass index], ASM [appendicular skeletal muscle mass]) was measured using DXA. Associations of baseline body composition with incident DM were assessed using Cox regression in the full cohort, with sensitivity analysis accounting for competing risk of death. Associations in long‐term subgroups and analysis of 14‐year and prediabetes changes were evaluated using multivariable logistic regression. Serum BCAAs were quantified by LC–MS for mediation analysis. Results Among 3421 participants (median age 72 years [IQR 68–76]; 50.1% female) without baseline DM, higher baseline adiposity (PBF: HR 1.613; FMI: HR 1.684; waist: 1.587) and ASM/ht &lt;jats:sup&gt;2&lt;/jats:sup&gt; (HR 1.561) were consistently associated with increased DM risk in adjusted Cox models (all &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.001). Conversely, higher relative muscle mass (ASM/weight: HR 0.603; ASM/BMI: HR 0.631; both &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.001) was associated with a lower risk. Faster gait speed was also linked to lower DM risk (HR 0.748, &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.001). Sensitivity analysis accounting for competing mortality demonstrated consistent results. In the complete 14‐year follow‐up subgroup ( &lt;jats:italic&gt;n&lt;/jats:italic&gt; = 937, 130 incident DM cases), key baseline associations were confirmed using logistic regression (e.g., ASM/weight: OR 0.633, &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.005). Analysis of 14‐year changes showed that attenuated loss of relative muscle mass (ΔASM/weight: OR 0.657; &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.005) was correlated with lower DM risk, whereas increased adiposity was correlated with higher risk (∆PBF: OR 1.509, &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.019). Pre‐DM changes over 0–4 years also revealed that early increases in waist (OR 1.428, &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.005) and declines in ASM/weight (OR 0.745, &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.013) were associated with subsequent DM. Serum BCAAs mediated 18.6%–38.2% of associations between baseline body composition and incident DM (all &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.01). No significant correlation was found between dietary protein intake and serum BCAAs after adjustment. Conclusions In older adults, higher baseline adiposity and lower relative muscle mass were associated with long‐term DM risk, while preserved muscle mass and faster gait speed were linked to a lower risk. These associations, partial","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"135 1","pages":"e70297"},"PeriodicalIF":8.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Sit‐ to‐ Stand Power From 2D Pose Estimation as an Indicator of Muscle Strength in Older Adults’","authors":"","doi":"10.1002/jcsm.70258","DOIUrl":"https://doi.org/10.1002/jcsm.70258","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"39 1","pages":"e20016"},"PeriodicalIF":8.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147681785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}