Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Improving Muscle Function Through a Multimodal Behavioural Intervention for Knee Osteoarthritis and Obesity: The POMELO Trial","authors":"Kristine Godziuk, Mary Forhan, Flavio T. Vieira, Joao F. Mota, Jason Werle, John A. Batsis, Lorenzo M. Donini, Mario Siervo, Carla M. Prado","doi":"10.1002/jcsm.70025","DOIUrl":"https://doi.org/10.1002/jcsm.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Treatments aimed at improving physical function and body composition, including reducing fat mass (FM) and increasing muscle mass, may benefit individuals with advanced knee osteoarthritis (OA) and obesity. We investigated the feasibility and efficacy of a multimodal behavioural intervention compared to usual care to enhance physical function and muscle mass in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The POMELO (Prevention Of MusclE Loss in Osteoarthritis) study is a two-arm pilot randomized controlled trial; NCT05026385. Participants aged 40–75 years, with a BMI ≥ 35 kg/m<sup>2</sup> and knee OA were randomized 1:1 to either the intervention group (POMELO) or usual care (UC). The 3-month POMELO intervention incorporated progressive resistance exercise (3 sessions/week), individualized nutrition counselling targeted for OA, and 12 group education sessions on nutrition and arthritis self-management. The UC group received standard clinical care. After the 3-month supervised intervention, both groups were followed for 6 months without support. Assessments at baseline, 3 months and 9 months (primary endpoint) included body composition (DXA, measuring FM and appendicular lean soft tissue [ALST]), physical function (chair-sit-to-stands [CSTS], 6-min walk [6MWT], maximal handgrip strength [HGS]), and health-related quality of life (Euroqol visual analog scale [EQ-5D VAS]). Co-primary outcomes were feasibility (intervention completion ≥ 80% and per-protocol adherence ≥ 60% [i.e., attendance at 12 education sessions and exercise 3 ×/week]) and acceptability (4-item Likert-scale satisfaction survey, and open-ended questions). Secondary outcomes included changes in physical function and ALST.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty participants were randomized (POMELO = 25, UC = 25), with 32 completing the study (69% female, mean age 64.9 ± 1.2 years, BMI 42.1 ± 1.0 kg/m<sup>2</sup>). The POMELO intervention group had 80% completion and 74% adherence, confirming feasibility. Higher satisfaction rates were observed in POMELO compared to UC (3.5 vs. 2.2, <i>p</i> < 0.001) indicating greater acceptability. The POMELO group had improvements in CSTS (mean difference [MD] 3.96, ES 1.2, <i>p</i> < 0.001), 6MWT (MD 31.6 m, ES 0.4, <i>p</i> = 0.039) and EQ-5D VAS (MD 7.9 points, ES = 0.4, <i>p</i> = 0.01) compared to UC. Both groups experienced FM loss, but only the UC group lost ALST and HGS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The POMELO intervention, combining personalized","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751234","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":"Assessing the Skeletal Muscle Pump During Lower Limb Counterpressure: Lags and Causality in Cardiovascular Regulation","authors":"Silvin P. Knight, Eoin Duggan, Feng Xue, Roman Romero-Ortuno","doi":"10.1002/jcsm.70019","DOIUrl":"https://doi.org/10.1002/jcsm.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Orthostatic hypotension (OH) is a prevalent condition among older adults, characterised by a sudden drop in blood pressure upon standing, often leading to dizziness and increased risk of falls, morbidity and mortality. The skeletal muscle pump is thought to be important in maintaining venous return and stabilising blood pressure during postural changes, especially during the performance of physical counterpressure manoeuvres (PCMs). This study investigated the temporal relationships between thigh muscle activation, thigh haemoglobin concentration and cardiovascular parameters (heart rate [HR], stroke volume [SV] and total peripheral resistance [TPR]) to understand the muscle pump's role in haemodynamic regulation while performing supine and standing PCMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-two participants (mean age 70.4 ± 5.2 years) were assessed at the Falls and Syncope Unit at St. James's Hospital, Dublin, Ireland. Each underwent an active stand test, around which participants were asked to squeeze their thigh muscles as hard as possible for 10 s, firstly while in the supine position, and secondly after standing. Surface electromyography (EMG), near-infrared spectroscopy (NIRS) and non-invasive digital artery photoplethysmography were used to continuously monitor thigh muscle activation, muscle haemoglobin concentration and cardiovascular function, respectively. Cross-correlation and Granger causality analyses were conducted to determine the temporal and causal relationships between the signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cross-correlation analysis revealed significant temporal relationships between muscle activation and cardiovascular parameters during PCMs. Specifically, HR, TPR and SV lagged EMG by approximately 1–3, 6–9 and 8–10 s, respectively. Mean peak cross-correlation coefficients during the standing PCM were 0.609 for EMG to HR, 0.516 for EMG to TPR and 0.564 for EMG to SV. Granger causality tests indicated that muscle activation significantly predicted changes in SV, HR and TPR, with causality proportions increasing during PCMs (e.g., SV to EMG: 9.1% during supine rest; EMG to SV: 63.6% during standing PCM). Notably, inter-individual variability was observed, with peak CCs for EMG to SV ranging from 0.251 to 0.849, and lag times from −21.9 to 13.4 s during standing PCM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings underscore the role of the skeletal muscle pump in modulating venous return and cardiac output during PCMs. The study provides ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740426","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":"Nut Intake, Functional Limitations, and Quality of Life in Older Adults: Findings From NHANES 2003–2012","authors":"Ilili Feyesa,&nbsp;Elena S. George,&nbsp;David Scott,&nbsp;Gavin Abbott,&nbsp;Jeew Hettiarachchi,&nbsp;Robin M. Daly,&nbsp;Jack Dalla Via,&nbsp;Ekavi N. Georgousopoulou,&nbsp;Sze-Yen Tan","doi":"10.1002/jcsm.70022","DOIUrl":"https://doi.org/10.1002/jcsm.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Increased nut consumption has positive effects on physical and cognitive function, but whether these translate into lower functional limitations in older adults is unknown. The aim of this study was to investigate the association between nut intake, functional limitations, the severity of these limitations and health-related quality of life (HRQOL) in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included data from 5807 adults (53.4% female) aged 60 years and older who participated in the US National Health and Nutrition Examination Survey (NHANES) between 2003 and 2012. Nut intake was assessed using two 24-h dietary recalls. Functional limitations were assessed using the NHANES Physical Functioning Questionnaire. Quality of life was evaluated using the four-question HRQOL-4 questionnaire. Negative binomial regression, linear regression and logistic regression analyses were used to examine associations between nut intake and both functional limitations and quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nut consumption (&gt; 0 g/day) was associated with significantly fewer functional limitations (β = −0.12; 95% CI: −0.24, −0.01; <i>p</i> = 0.048) and lower severity of these limitations (β = −0.67; 95% CI −1.11, −0.23; <i>p</i> = 0.004) compared to no consumption. Compared to nonconsumers, nut consumers (&gt; 0 g/day) also had lower odds of reporting poor physical health (OR = 0.81; 95% CI 0.68, 0.98; <i>p</i> = 0.027) and activity limitations (OR = 0.72; 95% CI 0.55, 0.95; <i>p</i> = 0.023). When participants were categorised by intake level (nonconsumers, &lt; 6.9 g/day, and ≥ 6.9 g/day), consuming ≥ 6.9 g/day was associated with fewer (β = −0.19; 95% CI: −0.32, −0.06; <i>p</i> = 0.004) and lower severity of functional limitations (β = −0.84; 95% CI: −1.30, −0.37; <i>p</i> = 0.001) compared to no consumption. Intake ≥ 6.9 g/day was also associated with lower odds of poor general health (OR = 0.76; 95% CI: 0.60, 0.906; <i>p</i> = 0.023), poor physical health (OR = 0.74; 95% CI: 0.57, 0.97; <i>p</i> = 0.027) and limitations in daily activities (OR = 0.61; 95% CI: 0.46, 0.82; <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Consumption of nuts, particularly at above-median levels, in older adults may be linked with experiencing fewer functional limitations, lower severity of these limitations and fewer general and physical unhealthy and inactive days.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740402","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":"Exogenous Nucleotides Supplementation Attenuates Age-Related Sarcopenia","authors":"Xin Wu,&nbsp;Rui Liu,&nbsp;Na Zhu,&nbsp;Xiujuan Wang,&nbsp;Chan Wei,&nbsp;Xiaoyang An,&nbsp;Meihong Xu,&nbsp;Yong Li","doi":"10.1002/jcsm.70002","DOIUrl":"https://doi.org/10.1002/jcsm.70002","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, an age-related clinical syndrome characterized by reduced skeletal muscle mass and strength, often leads to a loss of physical function. Nucleotides (NTs) supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that NTs declined in muscles with aging, and 5′-CMP, 5′-UMP can mitigate muscle atrophy in C2C12 myotubes. This study aimed to investigate the effects of NTs supplementation on sarcopenia and its possible mechanism.&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;Senescence-accelerated mouse prone-8 (SAMP8) mice and C2C12 cells were used to assess the effect of NTs on sarcopenia. We fed an NTs-enriched mixture to SAMP8 mice starting from the age of 3 months for 9 months or 15 months. NTs' effects on H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-induced C2C12 atrophy cells were tested using nucleotide monomers and mixtures. The body composition was measured by EchoMRI analysis meter. Physical performance was tested including grip strength, wire hang, horizontal bar and gait test. The immunofluorescence staining was used to evaluate the cross-sectional area (CSA) or type of muscle fibers and the diameter of myotubes. RT-qPCR, western blot, RNA sequencing (RNA-seq) and targeted metabolomic analyses were conducted to elucidate the underlying mechanisms.&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 results demonstrated that NTs significantly increased lean mass/body weight (&lt;i&gt;p&lt;/i&gt; &lt; 0.01, &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.434), the grip strength at 7 (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001, &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.312), 9 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.293) and 11 (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001, &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.507) months of age and the gait speed of mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001&lt;i&gt;, η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.3861). The immunofluorescence staining results indicated that NTs increased the CSA of muscle fibers (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001, &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.1081), especially for type IIb fibres. The RNA-seq results showed that NTs significantly downregulated the expression of sarcopenia-related genes (Trim63, Dkk3 and Mt1). The downregulation of Fbxo32, Trim63, Dkk3, Mt1 and p53 genes in NTs intervention group was confirmed by RT-qPCR and/or western blot (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Integrated analyses of RNA-seq and metabolomic showed that NTs could cause changes in metabolites, such as ketoleucine, 3-hydroxylisovalerylcarnitine and 3-methyl-2-oxovaleric acid, which could further regulate sarcopenia-related genes and inhibit protein degradation and promote protein synthesis. In vitro studies confirmed that NTs increased myotubes diameter and decreased expression of sarcopenia-related gen","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751637","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":"Comment on ‘Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis’ by Espino-Guarch et al.","authors":"Jinglin Li,&nbsp;Jiachen Peng","doi":"10.1002/jcsm.70037","DOIUrl":"https://doi.org/10.1002/jcsm.70037","url":null,"abstract":"&lt;p&gt;We have read with great interest the recent article by Espino-Guarch et al., ‘Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis’, a landmark study that significantly advances our understanding of skeletal muscle proteostasis [&lt;span&gt;1&lt;/span&gt;]. The authors present a compelling, albeit paradoxical, series of findings. They demonstrate that ablating the LAT2 transporter leads to intramuscular glutamine (Gln) accumulation, which in turn inhibits fasting-induced proteolysis in an mTORC1-dependent manner. This apparent preservation of muscle mass, however, comes at a steep and unexpected cost: the protective effect vanishes in complex disease states, and most strikingly, the mice exhibit a premature aging phenotype. This work provides a crucial insight into the intricate balance of metabolic regulation, and its paradoxical nature warrants a deeper discussion of the underlying mechanisms.&lt;/p&gt;&lt;p&gt;One of the most profound paradoxes presented is the dissociated nature of mTORC1 signalling. The authors elegantly show that mTORC1 is recruited to the lysosome, a canonical step for its activation by amino acids, which correctly correlates with the suppression of autophagy and proteasomal degradation [&lt;span&gt;1&lt;/span&gt;]. Yet this localized activation fails to produce a corresponding anabolic output. Global protein synthesis is not increased, and phosphorylation of the key translational repressor, 4E-BP1, is paradoxically decreased [&lt;span&gt;1&lt;/span&gt;]—the inverse of what canonical mTORC1 signalling would predict.&lt;/p&gt;&lt;p&gt;We contend that this phenomenon represents a ‘signal-outcome dissociation’, where the spatial and temporal context of the mTORC1 signal dictates its functional capacity. The chronic, Gln-driven accumulation of mTORC1 at the lysosome likely constitutes a low-grade, compartmentalized signal. This localized activity is sufficient to phosphorylate adjacent, catabolism-related substrates like the ULK1 complex, thereby inhibiting autophagy. However, it is critically insufficient to drive a global anabolic programme. Full anabolic activation, including robust phosphorylation of cytosolic targets like 4E-BP1 and S6K, requires the synergistic integration of multiple inputs, most notably potent growth factor signalling through the Akt-TSC-Rheb axis [&lt;span&gt;2, 3&lt;/span&gt;]. In the fasted state, where insulin signalling is minimal, the Gln-driven signal exists in a functional vacuum. This creates a metabolic stalemate: catabolism is switched off, but anabolism cannot be fully switched on. This highlights a critical principle: the mere activation of a kinase at one cellular location does not guarantee the execution of all its downstream programmes.&lt;/p&gt;&lt;p&gt;The internal paradoxes of the LAT2KO muscle manifest as profound external consequences. The authors frame the concurrently accelerated lipolysis in their mice as a potential study limitation [&lt;span&gt;1&lt;/span&gt;]. We posit this is not a limitation but a co","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725685","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 Data and Predictors of HR-pQCT-Derived Muscle Density and Its Prediction of Physical Performance","authors":"Stuart J. Warden,&nbsp;Ziyue Liu,&nbsp;Robyn K. Fuchs,&nbsp;Lilly G. Davisson,&nbsp;Keith G. Avin,&nbsp;Erik A. Imel,&nbsp;Kenneth Lim,&nbsp;Sharon M. Moe,&nbsp;Rachel K. Surowiec","doi":"10.1002/jcsm.70029","DOIUrl":"https://doi.org/10.1002/jcsm.70029","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;There is increasing awareness of a role for muscle composition in sarcopenia and cachexia. Computed tomography (CT)–based measures of muscle density (MusD) are commonly used to indicate composition, with a decrease in MusD reflecting an increase in muscle fat infiltration. The current study explored predictors of MusD acquired using high-resolution peripheral quantitative computed tomography (HR-pQCT) and whether MusD predicted physical performance. In addition, reference data for MusD were generated and applied.&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;HR-pQCT scans performed in 1662 adults (aged 18–80 years) at 30% of bone length proximal from the distal end of the radius and tibia were analysed for forearm and leg MusD, respectively. Predictors of MusD were explored, and it was investigated whether MusD predicted physical performance. Centile curves were fit to the MusD data using the LMS approach to generate reference data, and a calculator was developed to enable computation of subject-specific standardised outcomes. The utility of the calculator was explored in validation cohorts of female collegiate-level athletes (&lt;i&gt;n&lt;/i&gt; = 50) and individuals with chronic kidney disease (CKD) (&lt;i&gt;n&lt;/i&gt; = 50).&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;Forearm and leg MusD were predicted by whole-body percent fat, sex and age. Forearm and leg MusD were 0.46 (~1.9%) and 0.60 mgHA/cm&lt;sup&gt;3&lt;/sup&gt; (~2.6%) lower in females than in males, respectively (all &lt;i&gt;p&lt;/i&gt; ≤ 0.002). For every decade of greater age, forearm and leg MusD were 0.28 (~1.2%) and 0.75 mgHA/cm&lt;sup&gt;3&lt;/sup&gt; (~3.3%) lower, respectively (all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). These observations were independent of whole-body percent fat and appendicular lean mass (ALM)/height&lt;sup&gt;2&lt;/sup&gt;. MusD predicted grip strength, fast gait speed and self-reported physical function independent of ALM/height&lt;sup&gt;2&lt;/sup&gt;, body mass index and whole-body percent fat. Grip strength was 0.756 kg (~2.4%) greater for every 1 mgHA/cm&lt;sup&gt;3&lt;/sup&gt; (~4.2%) greater forearm MusD (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Reference data were generated. Compared to the reference data, female athletes had above-average leg MusD (&lt;i&gt;z&lt;/i&gt;-score = 0.20; 95% CI, 0.01–0.39), whereas those with CKD had &lt;i&gt;z&lt;/i&gt;-scores for forearm and leg MusD of −1.51 (95% CI, −1.95 to −1.08) and −1.70 (95% CI, −2.04 to −1.36), respectively.&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;HR-pQCT acquired MusD provides a novel indicator of muscle composition which predicts physical function independent of muscle quantity (i.e., ALM","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725683","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":"CircGLIS3 Inhibits Intramuscular Adipogenesis and Alleviates Skeletal Muscle Fat Infiltration","authors":"Shengchen Yu,&nbsp;Jianfang Wang,&nbsp;Haibing Liu,&nbsp;Juntao Guo,&nbsp;Abebe Belete Kuraz,&nbsp;Yueting Pan,&nbsp;Anning Li,&nbsp;Chugang Mei,&nbsp;Gong Cheng,&nbsp;Linsen Zan","doi":"10.1002/jcsm.70009","DOIUrl":"https://doi.org/10.1002/jcsm.70009","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;Intramuscular fat (IMF) is a key determinant of meat quality. Excessive IMF deposition, commonly observed in human obesity and aging, negatively affects skeletal muscle function. Circular RNAs (circRNAs) play critical regulatory roles in muscle and fat development, as well as in the progression of related diseases. However, the specific functions and underlying mechanisms of circRNAs in IMF deposition have not been extensively studied.&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 screened adipogenic differentiation-related circRNAs using circRNA-seq combined with WGCNA. Functional analyses, including loss-of-function and gain-of-function experiments, were performed to determine the role of &lt;i&gt;circGLIS3&lt;/i&gt; in regulating adipogenesis in bovine intramuscular preadipocytes and 3T3-L1 cells. A high-fat diet-induced mouse model was established to investigate the in vivo effects of &lt;i&gt;circGLIS3&lt;/i&gt; on skeletal muscle fat infiltration in mice (C57BL/6; &lt;i&gt;n&lt;/i&gt; = 6 males). Mechanistic studies involved transcriptomic analysis, dual-luciferase reporter assays, RNA immunoprecipitation, and rescue 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;We screened and characterized a novel circRNA, &lt;i&gt;circGLIS3&lt;/i&gt;, which is highly expressed in bovine IMF tissue and in the skeletal muscle of mice exhibiting fat infiltration. Functionally, &lt;i&gt;circGLIS3&lt;/i&gt; overexpression inhibited triglyceride synthesis (−16.19%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and lipid droplet accumulation (−42.44%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) in intramuscular preadipocytes, concurrently downregulating the expression of key adipogenesis-related genes and proteins (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). &lt;i&gt;CircGLIS3&lt;/i&gt; knockdown promoted triglyceride synthesis (+28.32%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and lipid droplet accumulation (+47.40%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) in intramuscular preadipocytes, accompanied by a significant upregulation of adipogenesis-related genes and proteins (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Notably, &lt;i&gt;circGLIS3&lt;/i&gt; exhibits more than 80% sequence homology among bovine, mouse, and human species. &lt;i&gt;CircGLIS3&lt;/i&gt; overexpression inhibited triglyceride synthesis (−28.84%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and lipid droplet accumulation (−46.49%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) in 3T3-L1 cells, concurrently downregulating the expression of adipogenesis-related genes and proteins (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Overexpression of &lt;i&gt;circGLIS3&lt;/i&gt; reduced skeletal muscle fat infiltration induced by high-fat diet in mice (−57.88%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Mechanistically, &lt;i&gt;circGLIS3&lt;/i&gt; acts as a sponge for miR-21-3p, increasing the expression of its target gene, &lt;i&gt;LEPR&lt;/i&gt; (+56.05%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), and promoting the phosphory","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725684","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":"Six-Minute Walk Test Is Superior to Grip Strength as a Marker of Functional Recovery During Cancer Cachexia Rehabilitation","authors":"Addison Barber,&nbsp;Amber Willbanks,&nbsp;Kathryn Abplanalp,&nbsp;Christopher W. Lewis,&nbsp;Ben Binder-Markey,&nbsp;Prakash Jayabalan,&nbsp;Richard L. Lieber,&nbsp;Ishan Roy","doi":"10.1002/jcsm.70024","DOIUrl":"https://doi.org/10.1002/jcsm.70024","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;Decline in functional independence is a defining event of cancer cachexia, and attempts at creating cachexia-specific therapies have largely failed because of the inability to identify treatments that improve functional capacity. This may be, in part, due to a lack of outcomes that are appropriate and sensitive enough to detect functional recovery. Grip strength is a frequently used outcome measure in cachexia clinical studies; however, the use of gait-based measures is now emerging. These two outcome measures have never been directly compared in the same cohort of cachexia patients regarding their ability to measure and relationship to functional independence. We hypothesize that gait-based measures more comprehensively act as a proxy measure for functional independence related to 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;In a retrospective cohort study of 485 cancer patients with a range of cachexia severity and related functional decline who required care at a single-centre inpatient rehabilitation facility (IRF), we assessed the six-minute walk test (6MWT) and hand grip strength (hGS) as proxy measures for functional capacity. Functional capacity is defined as mobility and activities of daily living (ADLs), is quantified by measures of functional independence and referred to here as the Total Motor Score. Cachexia patients were identified primarily using the Fearon et al. consensus criteria, with secondary identification by the Weight Loss Grading Scale (WLGS), Prognostic Nutritional Index (PNI) and neutrophil-to-lymphocyte ratio (NLR). Primary outcomes were change/gain in Total Motor Score, IRF discharge destination (e.g., homebound status or need for care facility) and 6-month survival.&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 presence of cachexia in this cohort was 63%. This cohort was 52% male. Mean age was 63 ± 0.63 (SEM) years. Multivariate linear regression demonstrated that change in 6MWT (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) but not hGS (&lt;i&gt;p&lt;/i&gt; = 0.084) correlated with Total Motor Score gain after controlling for age, disease burden, cancer type, previous cancer treatment and baseline motor function as covariates. Area under the curve analysis revealed that change in 6MWT (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001, AUC = 0.77) was a stronger predictor of Total Motor Score gain than hGS (&lt;i&gt;p&lt;/i&gt; = 0.0016, AUC = 0.59). In a multivariate logistic regression model, discharge from IRF to home with independence was predicted by change in 6MWT (&lt;i&gt;p&lt;/i&gt; = 0.0007) but not hGS (&lt;i&gt;p&lt;/i&gt; = 0.8075). Six-month survival post-rehabilitation was predicted by change in 6MWT (&lt;i&gt;p&lt;/i&gt; = 0.0345) but not hGS (&lt;i&gt;p&lt;/i&gt; = 0.90","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716632","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":"Unravelling the Role of PIEZO1 in Adipogenesis of Fibrogenic/Adipogenic Progenitors for Muscle Fat Infiltration After Rotator Cuff Tear","authors":"Xingzuan Lin,&nbsp;Qingfa Song,&nbsp;Amila Kuati,&nbsp;Zhanghua Li,&nbsp;Hao Zhou,&nbsp;Shujing Feng,&nbsp;Minhui Wang,&nbsp;Siyuan Zhu,&nbsp;Guoqing Cui,&nbsp;Jianhua Wang,&nbsp;Xiexiang Shao","doi":"10.1002/jcsm.70004","DOIUrl":"https://doi.org/10.1002/jcsm.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscular fatty infiltration originated from fibrogenic/adipogenic progenitors (FAPs) is a common issue following rotator cuff tear (RCT) that impairs shoulder function. RCT disrupted the biomechanical equilibrium of the shoulder and decreased the mechanical stimuli transmitted to the rotator cuff. Whether mechanical stimuli participate in mediating muscular fatty infiltration after RCT remains unknown. The current study aimed to explore how mechanical environment changes caused by RCT affect muscular fatty infiltration and to identify the potential therapeutic modality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human and murine FAPs were isolated from RCT and control (CTRL) groups to compare adipogenesis properties. Single-cell RNA sequencing and bulk RNA sequencing were performed to investigate the mechanisms of excessive adipogenesis of FAPs after RCT. The effects and mechanisms of PIEZO1 on adipogenesis of FAPs were investigated by small-molecule treatment and FAP-specific PIEZO1 knockout mice. The antiadipogenic effects of low-intensity pulsed ultrasound (LIPUS) were investigated in vitro and in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the adipogenic differentiation ability of FAPs was increased after RCT (1.9-fold vs. CTRL, <i>p</i> &lt; 0.05). Single-cell RNA-sequencing data analyses and confirmation assays revealed suppressed expression of PIEZO1, which was proved by real-time qPCR and Western blot (2.9-fold vs. CTRL, <i>p</i> &lt; 0.01, and 3.4-fold vs. CTRL, <i>p</i> &lt; 0.01). There was increased PPARG expression and adipogenesis ability of FAPs after PIEZO1 ablation (1.7-fold vs. CTRL, <i>p</i> &lt; 0.01, and 2.3-fold vs. CTRL, <i>p</i> &lt; 0.01). The PIEZO1-mediated antiadipogenic role by ERK/KLF4 signalling was confirmed by small-molecule treatment and <i>PIEZO1 KO</i> mice evaluation. LIPUS could reactivate PIEZO1 and mitigate the adipogenesis of FAPs in vitro, ameliorate the muscular fatty degeneration after RCT (3.0-fold vs. CTRL, <i>p</i> &lt; 0.001) and facilitate the improvement of shoulder functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that the downregulation of PIEZO1 expression contributes to the enhanced adipogenesis capacity of FAPs after RCT by inhibiting ERK/KLF4 signalling. LIPUS could mitigate the excessive adipogenesis of FAPs by upregulating expression of PIEZO1, alleviate muscular fatty infiltration and improve shoulder function after RCT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716633","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":"Motoric Cognitive Risk Syndrome Associated With Risk of Frailty and Likelihood of Reversion in Older Adults","authors":"Dingchun Hou,&nbsp;Bo Liang,&nbsp;Lijun Pei,&nbsp;Gong Chen","doi":"10.1002/jcsm.70033","DOIUrl":"https://doi.org/10.1002/jcsm.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Motoric cognitive risk syndrome (MCR), a predementia condition, is reported to be associated with frailty. However, the associations of MCR with frailty risk and its reversibility remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A longitudinal study was conducted of 10 809 older adults from the Health and Retirement Study in the United States. Frailty was assessed by the frailty index and reversibility was measured by transitions from frailty at baseline to non-frailty during follow-up. MCR was defined as the presence of both subjective cognitive complaints and slow gait speed in individuals without dementia or mobility disability. Multistate Markov models were performed to evaluate the effects of MCR on transitions among non-frailty, frailty and death. Cox regression models were used to estimate MCR associated with the risk of frailty and the likelihood of reversion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 10 809 participants with a median age of 71 (interquartile range: 67–71) years and 6462 (57.93%) females, a total of 105 372 person-years (9.75 years in average) were followed up. The prevalence of MCR at baseline in non-frail and frail participants was 3.12% and 18.56%, respectively. Compared with non-MCR, MCR increased the probability of transitioning from non-frailty to frailty by 46% (HR = 1.46, 95% CI: 1.27–1.67) and decreased the probability of transitioning from frailty to non-frailty by 36% (HR = 0.64, 95% CI: 0.52–0.77). Compared with normal function, subjective cognitive complaints only, slow gait speed only and MCR increased the probability of transitioning from non-frailty to frailty by 43% (HR = 1.43, 95% CI: 1.33–1.53), 14% (HR = 1.14, 95% CI: 1.00–1.30) and 69% (HR = 1.69, 95% CI: 1.47–1.96) and decreased the probability of transitioning from frailty to non-frailty by 18% (HR = 0.82, 95% CI: 0.74–0.92), 27% (HR = 0.73, 95% CI: 0.60–0.88) and 45% (HR = 0.55, 95% CI: 0.45–0.67), respectively. As shown in the prospective analyses, MCR and its single component were associated with increased frailty risk and decreased likelihood of reversion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MCR is associated with an increased risk of frailty, accelerated transition from non-frailty to frailty and a decreased likelihood of reversion from frailty. MCR emerges as a promising risk stratification factor for frailty, highlighting the need for increased focus on individuals with MCR, particularly within the pre-frail population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 4","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716944","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}