Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis","authors":"Meritxell Espino-Guarch, Susie Shih Yin Huang, Clara Vilches, Esther Prat, Rana El Nahas, Ghalia Missous, Susanna Bodoy, Abbirami Sathappan, Mohammad Ameen Al-Aghbar, Clara Mayayo, Montse Olivé, Silvia Busquets-Rius, David Sebastián, Antonio Zorzano, Manuel Palacin, Nicholas van Panhuys, Virginia Nunes","doi":"10.1002/jcsm.13847","DOIUrl":"https://doi.org/10.1002/jcsm.13847","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The neutral amino acid transporter <i>SLC7A8</i> (LAT2) has been described as a key regulator of metabolic adaptation. LAT2 mutations in human populations have been linked to the early onset of age-related hearing loss and cataract growth. As LAT2 was previously found to be highly expressed in skeletal muscle, here we characterised its role in the regulation of <i>skeletal muscle</i> amino acid flux and metabolic adaptation to fasting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type (WT) and LAT2 knock-out (LAT2KO) mice were exposed to short- and long-periods of fasting (16 and 48 h). The impact of the absence of LAT2 on amino acid content, gene expression, proteolysis activity, muscle tone, and histology was measured. To characterise the impact on muscle degradation, we tested LAT2 KO mice in cancer-associated cachexia, streptozocin-induced Type-1 diabetes, and ageing models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LAT2KO mice experienced a notable reduction in body weight during fasting (WT:14% and LAT2KO:18%, <i>p</i> = 0.02), with a greater reduction in fat mass (0.5-fold, <i>p</i> = 0.013) and a higher relative retention of muscle mass (1.3-fold, <i>p</i> = 0.0003) compared with WT. The absence of LAT2 led to increased intramuscular glutamine (Gln) accumulation (6.3-fold, <i>p</i> < 0.0001), accompanied by a reduction in skeletal muscle proteolysis during fasting (0.61-fold, <i>p</i> = 0.0004) primarily due to decreased proteasomal and autophagic activity (0.45-fold, <i>p</i> = 0.016 and 0.7-fold, <i>p</i> = 0.002, respectively). Ex vivo incubation of LAT2KO muscle with rapamycin recovered proteolysis function, demonstrating a mTORC1-dependent pathway. Decreased proteolysis in LAT2KO animals was associated with increased mTORC1 translocation to the lysosome (mTORC1-Lamp1 colocalization in fasted LAT2KO muscles was 1.23-fold, <i>p</i> < 0.0001). Of the three muscle loss models tested, differences were observed only during ageing. Young LAT2KO mice (3 M) exhibited muscle tone and MurF1 expression levels comparable to those of older WT mice (12 M) (0.44-fold, <i>p</i> = 0.02 and 0.48-fold, <i>p</i> = 0.04, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LAT2 has a critical role in regulating Gln efflux from skeletal muscle. The absence of LAT2 led to elevated intracellular Gln levels, impairing muscle proteolysis by inducing mTORC1 recruitment to the lysosome. Further, chronic Gln accumulation and decreased proteolysis were found to induce the early onset of an age-relate","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339581","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":"Adherence to Physical Activity and Incident Mobility Disability in Older Adults With Mobility Limitations","authors":"Alejandro Álvarez-Bustos, Helio José Coelho-Junior, Riccardo Calvani, Leocadio Rodriguez-Mañas, Matteo Tosato, Matteo Cesari, Antonio Cherubini, Alfonso J. Cruz-Jentoft, Pálmi V. Jónsson, Fabrizia Lattanzio, Marcello Maggio, Regina Roller-Wirnsberger, Ingrid Rýznarová, Annemie M. W. J. Schols, Cornel C. Sieber, Alan J. Sinclair, Anna Skalska, Timo Strandberg, Achille Tchalla, Eva Topinková, Bruno Vellas, Stephan von Haehling, Francesco Landi, Emanuele Marzetti, for the SPRINTT consortium","doi":"10.1002/jcsm.13870","DOIUrl":"https://doi.org/10.1002/jcsm.13870","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preservation of mobility independence is a primary goal in older adults with physical frailty and sarcopenia (PF&S). Interventions based on the combination of physical activity (PA) and nutritional counselling have been indicated as strategies for the management of this condition, although their effectiveness is not confirmed in all investigations. A possible explanation for this uncertain scenario relies in the impact of the adherence to PA interventions. Hence, the present study investigated the impact of the adherence to PA sessions on the incidence of mobility disability in older adults with PF&S.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a secondary analysis of an evaluator blinded, randomised controlled trial, developed in 16 clinical sites across 11 European countries, from January 2016 to 31 October 2019. Participants were community-dwelling older adults (70+ years) with PF&S enrolled in the SPRINTT trial (NCT02582138). PF&S was operationalised as having a total score from 3 to 9 on the short physical performance battery (SPPB), low appendicular lean mass and ability to complete the 400-m walk test in < 15 min. Data from participants allocated to a multicomponent intervention (PA with technological support plus nutritional counselling) and a healthy ageing lifestyle education programme (control group) were analysed. Adherence to PA was assessed based on the number of weekly sessions attended. According to recommendations of the American College of Sports Medicine, adherence was categorised as below recommendations (< 2 sessions/week, BR), meeting recommendations (2–3 sessions/week, MR), and above recommendations (> 3 sessions/week, AR). The primary outcome was incident mobility disability, operationalised as incident inability to complete the 400-m walk test in < 15 min during up to 36 months of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data of 1444 participants (mean age 79.3 years, 72.6% women) were analysed. In those with SPPB scores of 3–7, MR and AR groups had lower risk of mobility disability compared with controls [MR HR (95% CI): 0.57 (0.41–0.78), <i>p</i> = 0.001; AR HR (95% CI): 0.33 (0.23–0.46), <i>p</i> < 0.001] and BR groups [MR: HR (95% CI): 0.48 (0.34–0.69), <i>p</i> < 0.001; AR: HR (95% CI): 0.27 (0.18–0.38), <i>p</i> < 0.001] in a dose-dependent manner. In those with SPPB scores of 8 or 9, the BR group had a higher risk of mobility disability than controls. MR and AR groups had a lower risk of mobility disability than the BR group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315254","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":"Development and Validation of Quantile Regression Forests for Prediction of Reference Quantiles in Handgrip and Chair-Stand Test","authors":"Giulia Giordano, Luca Mastrantoni, Francesco Landi, The Lookup 8+ Study Group","doi":"10.1002/jcsm.13868","DOIUrl":"https://doi.org/10.1002/jcsm.13868","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle strength is one of the key components in the diagnosis of sarcopenia. The aim of this study was to train a machine learning model to predict reference values and percentiles for handgrip strength and chair-stand test (CST), in a large cohort of community dwellers recruited in the Longevity check-up (Lookup) 8+ project.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The longevity checkup project is an ongoing initiative conducted in unconventional settings in Italy from 1 June 2015. Eligible participants were 18+ years and provided written informed consent. After a 70/20/10 split in training, validation and test set, a quantile regression forest (QRF) was trained. Performance metrics were <i>R</i>-squared (<i>R</i><sup>2</sup>), mean squared error (MSE), root mean squared error (RMSE) and mean Winkler interval score (MWIS) with 90% prediction coverage (PC). Metrics 95% confidence intervals (CI) were calculated using a bootstrap approach. Variable contribution was analysed using SHapley Additive exPlanations (SHAP) values. Probable sarcopenia (PS) was defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between 1 June 2015 and 23 November 2024, a total of 21 171 individuals were enrolled, of which 19 995 were included in our analyses. In the overall population, 11 019 (55.1%) were females. Median age was 56 years (IQR 47.0–67.0). Five variables were included: age, sex, height, weight and BMI. After the train/validation/test split, 13 996 subjects were included in the train set, 4199 in validation set and 1800 in the test set. For handgrip strength, the <i>R</i><sup>2</sup> was 0.65 (95% CI 0.63–0.67) in the validation set and 0.64 (95% CI 0.62–0.67) in the test set. PCs were 91.5% and 91.2%, respectively. For CST test, the <i>R</i><sup>2</sup> was 0.23 (95% CI 0.20–0.25) in the validation set and 0.24 (95% CI 0.20–0.28) in the test set. The PCs were 89.5% and 89.3%. Gender was the most influential variable for handgrip and age for CST. In the validation set, 23% of subjects in the first quartile for handgrip and 13% of subjects in the fourth quartile for CST test met criteria of PS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We developed and validated a QRF model to predict subject-specific quantiles for handgrip and CST. These models hold promise for integration into clinical practice, facilitating cost-effective and time-efficient early identification of individuals at elevated risk of sarcopenia. The pre","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13868","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Trial of Nutrition and Exercise Treatment in Patients With Pancreatic and Non-Small Cell Lung Cancer (NEXTAC-TWO)","authors":"Shuichi Mitsunaga, Tateaki Naito, Hisao Imai, Madoka Kimura, Satoru Miura, Hisashi Tanaka, Takuro Mizukami, Akira Imoto, Chihiro Kondoh, Hiroyuki Okuyama, Makoto Ueno, Shinsuke Shiotsu, Toshimi Inano, Haruka Chitose, Noriatsu Tatematsu, Taro Okayama, Takako Mouri, Miwa Sugiyama, Katsuhiro Omae, Takanori Kawabata, Keita Mori, Koichi Takayama","doi":"10.1002/jcsm.13871","DOIUrl":"https://doi.org/10.1002/jcsm.13871","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In our previous study (NEXTAC-ONE), the Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) program (including home-based exercise and branched-chain amino acid-containing supplements combined with nutritional counselling) was shown to potentially prevent low muscle mass-related disability in elderly cancer patients. This randomized controlled trial (NEXTAC-TWO) was conducted to elucidate whether the NEXTAC program prolongs disability-free survival in elderly patients with advanced pancreatic or non-small cell lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This open-label, multicentre, randomized phase II study was conducted at 15 Japanese hospitals. Patients aged ≥ 70 years, with pathologically proven advanced pancreatic or non-small cell lung cancer, who were scheduled to undergo systemic chemotherapy for treatment-naïve tumours were randomly assigned (1:1) to undergo observation or receive the NEXTAC program for 12 weeks. Randomization was performed by the minimization method, using performance status and types with cancer diagnosis and anticancer treatment as adjustment factors. The primary endpoint was disability-free survival (period from randomization to the date patients were evaluated as needing care or death due to any cause). Key secondary endpoints were change in weight, muscle mass, physical activity, nutritional assessment, safety and survival. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028801).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2017 to 2019, 131 patients were enrolled and randomly assigned to NEXTAC (<i>n</i> = 66) or control arms (<i>n</i> = 65, median age 76.0 years). After randomization, two patients in the NEXTAC arm declined further participation. As a result, 64 patients (median age 75.5 years) received at least one session of the NEXTAC program. The completion rate of the planned exercise and nutrition consultation sessions was 98.4% in the NEXTAC arm. Of the 129 patients, 91 (71%) had a disability (44 in the NEXTAC arm; 47 in the control arm). In the primary analysis, median disability-free survival periods were 478 days (95% confidence interval [CI], 358–576) in the NEXTAC arm and 499 days in the control arm (95% CI, 363–604), with no significant differences between them (<i>p</i> = 0.884). The hazard ratio for disability-free survival in the NEXTAC arm compared with the control arm was 0.970 (95% CI 0.642–1.465). There were no differences in the secondary endpoints between the two arms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299785","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":"Parameters of Body Composition Predict Clinical Course in Acute Colonic Diverticulitis","authors":"Alexey Surov,&nbsp;Mattes Hinnerichs,&nbsp;Iram Shahzadi,&nbsp;Nina P. Haag,&nbsp;Jan Robert Kröger,&nbsp;Berthold Gerdes,&nbsp;Saleem Elhabash,&nbsp;Jan Borggrefe","doi":"10.1002/jcsm.13864","DOIUrl":"https://doi.org/10.1002/jcsm.13864","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute colonic diverticulitis (ACD) is the most common complication of colonic diverticulosis. Body composition, that is, proportion, distribution and quality of muscle and adipose tissues may play a relevant role in ACD. Previously, only few reports with small number of patients analysed the prognostic role of body composition in ACD. Our purpose was to analyse associations between the occurrence of complications and parameters of body composition in patients with ACD in a large sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 646 patients with ACD. The duration of hospital stay (days) and occurrence of complications were recorded. Parameters of body composition were semiautomatically measured with the freely available ImageJ software. Skeletal muscle area (SMA), skeletal muscle density, visceral adipose tissue (VAT), subcutaneous adipose tissue and intramuscular adipose tissue were estimated. To assess the impact of body composition parameters on ACD complications, Cox regression model (adjusted for sex and age) was used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Low skeletal muscle area (sarcopenia) was found in 322 patients (49.8%). High VAT was observed in 525 patients (81.3%). Low skeletal muscle density or myosteatosis was identified in 322 patients (49.8%). Length of hospital stay was prolonged in patients with sarcopenia, myosteatosis and/or visceral adiposity. Sarcopenia was an independent predictor for occurrence of complicated ACD, OR = 1.48, 95% CI (1.03–2.13), <i>p</i> = 0.033. Myosteatosis predicted occurrence of free perforation, OR = 2.36, 95% CI (1.01–5.43), <i>p</i> = 0.033. Furthermore, visceral adiposity tended to be a strong predictor of free perforation, OR = 7.62, 95% CI (1.29–138.00), <i>p</i> = 0.05. Finally, sarcopenia predicted occurrence of macro abscesses, OR = 2.41, 95% CI (1.41–4.26), <i>p</i> = 0.002.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with sarcopenia, myosteatosis and visceral adiposity have prolonged length of hospital stay. Macro abscesses occur more frequently in patients with sarcopenia. Myosteatosis and high VAT are associated with free perforation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13864","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299786","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":"Low Relative Sit-to-Stand Power Is Associated With the Development of Adverse Health Outcomes: A 5-Year Longitudinal Study","authors":"Mikel Garcia-Aguirre,&nbsp;Ivan Baltasar-Fernandez,&nbsp;Julian Alcazar,&nbsp;Ana Alfaro-Acha,&nbsp;F. A. Bareiro-Quiñonez,&nbsp;Ignacio Ara,&nbsp;Leocadio Rodriguez-Mañas,&nbsp;Francisco J. Garcia-Garcia,&nbsp;Luis M. Alegre","doi":"10.1002/jcsm.13852","DOIUrl":"https://doi.org/10.1002/jcsm.13852","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Relative sit-to-stand (STS) power has emerged as a key biomarker of aging due to its strong association with adverse health outcomes such as frailty or disability. Thus, this study aimed to evaluate the association between low baseline relative STS power with the development of adverse health outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 839 community-dwelling older adults (65–91 years; 42% men) from the Toledo Study for Healthy Aging were assessed at baseline and after 5 years of follow-up. Relative STS power was assessed using the 30-s STS test and Alcazar's equation. Adverse conditions considered encompassed frailty (evaluated using the frailty trait scale 5 [FTS5] or frailty phenotype [FP]), disability in basic (BADL; Barthel index) and instrumental activities of daily living (IADL; Lawton and Brody scale), cognitive impairment (mini-mental state examination), depression (geriatric depression scale) and medication use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, people with low relative STS power (461 participants) had significantly higher FTS5 (+5.9 points), FP (+0.56 criteria), disability in BADL (−0.1 points) and IADL (−0.7 points), cognitive impairment (−1.3 points) and medication use (+0.9 medications) than older adults with normal relative STS power (all <i>p</i> &lt; 0.05). In contrast, no significant differences were observed at baseline in GDS (<i>p</i> &gt; 0.05). Low baseline relative STS power was significantly associated with the incidence of frailty FTS5 (OR [95% CI] = 2.51 [1.26–5.03]; <i>p</i> = 0.009), disability in BADL (OR [95% CI] = 1.70 [1.13–2.56]; <i>p</i> = 0.011) and IADL (OR [95% CI] = 1.79 [1.06–3.02]; <i>p</i> = 0.030) and increased medication use (OR [95% CI] = 1.51 [1.10–2.07]; <i>p</i> = 0.011) during the follow-up. No association was found with the incidence of frailty by FP (OR [95% CI] = 1.71 [0.75–3.93]; <i>p</i> = 0.202), depression (OR [95% CI] = 1.29 [0.85–1.98]; <i>p</i> = 0.236) or cognitive impairment (OR [95% CI] = 1.38 [0.86–2.21]; <i>p</i> = 0.178).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Participants with low relative STS power exhibited worse baseline and 5-year follow-up values in frailty, BADL and IADL disability, cognitive impairment and medication intake. Low relative STS power was also associated with a higher probability of future frailty, disability in BADL and IADL and increased medication use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299790","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":"Polygonati Rhizoma Prevents Glucocorticoid-Induced Growth Inhibition of Muscle via Promoting Muscle Angiogenesis Through Deoxycholic Acid","authors":"Shiyi Shi,&nbsp;Rui Li,&nbsp;Yanxu Han,&nbsp;Jiahao Xie,&nbsp;Shaoshuai Wang,&nbsp;Jie Liu,&nbsp;Fangyan Wan,&nbsp;Gaifeng Hou,&nbsp;Zuhong Liu,&nbsp;Xiaobo Sun,&nbsp;Bo Zuo,&nbsp;Zhihao Jia,&nbsp;Zhinan Mei,&nbsp;Tongxing Song","doi":"10.1002/jcsm.13853","DOIUrl":"https://doi.org/10.1002/jcsm.13853","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucocorticoids are commonly used in clinical treatments but can cause muscle growth inhibition and weakness at high doses. The mechanisms and treatments for glucocorticoid-induced muscle growth inhibition remain poorly understood. This study aims to investigate the anti-atrophic effects of <i>Polygonati Rhizoma</i> (PR) and a mixture of low-dose fructose and glucose (MFG, an active component mimic in PR) on skeletal muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6 mice (3-week-old, <i>n</i> = 8) were gavaged with aqueous extract of PR (AEPR). MFG was used to gavage normal male C57BL/6 mice (3-week-old, <i>n</i> = 10) and male C57BL/6 mice with dexamethasone (DEX)-induced muscle growth inhibition (3-week-old, <i>n</i> = 7). After 2 weeks of gavage, the body weight and muscle mass of the mice were measured. Intestinal content was collected, the concentration of deoxycholic acid (DCA) was analysed and gut microbiota changes were assessed through 16S rRNA gene sequencing. Muscle angiogenesis was examined through the expression of vascular endothelial growth factors (VEGFs), focusing on the DCA-activated TGR5/cAMP/PKA/pCREB pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AEPR significantly increased the body weight (22.90 ± 0.90 vs. 21.83 ± 0.87 g, *<i>p</i> &lt; 0.05) and grip strength (1.32 ± 0.11 vs. 1.04 ± 0.12 N, ***<i>p</i> &lt; 0.001) of mice. MFG (0.5 g/kg body weight) also significantly elevated the body weight (21.44 ± 0.71 vs. 20.14 ± 0.82 g, **<i>p</i> &lt; 0.01) and muscle mass (0.37 ± 0.018 vs. 0.33 ± 0.035 g, **<i>p</i> &lt; 0.01) of mice. In the DEX group, MFG restored the DCA level (log₂[intensity]) in intestinal content (25.41 ± 1.64 vs. 22.69 ± 0.74, *<i>p</i> &lt; 0.05) and increased the abundance of <i>Collinsella aerofaciens</i> as measured by DNA concentration (0.80 ± 0.64 vs. 0.24 ± 0.09 pg/μL, <i>p</i> = 0.096). Mechanistically, MFG upregulated VEGFs expression and promoted muscle angiogenesis via the TGR5/cAMP/PKA/pCREB pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that AEPR and its active component mimic MFG can promote muscle growth and MFG mitigates muscle growth inhibition by modulating gut microbiota and enhancing muscle angiogenesis. These findings suggest that fructose-containing treatments are novel strategies to address skeletal muscle dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292702","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 “Intermittent Hypoxic–Hyperoxic Training During Inpatient Rehabilitation Improves Exercise Capacity and Functional Outcome in Patients With Long Covid: Results of a Controlled Clinical Pilot Trial” by Doehner et al.—The Authors' Reply","authors":"Wolfram Doehner,&nbsp;Per Otto Schueller","doi":"10.1002/jcsm.13866","DOIUrl":"https://doi.org/10.1002/jcsm.13866","url":null,"abstract":"&lt;p&gt;In their letter to the editor, Kulka and Tryba discuss a recent clinical pilot study investigating the efficacy and safety of intermittent hypoxic–hyperoxic training (IHHT) and raise concerns that the nonrandomized group allocation in this study may limit the generalizability of the findings to broader patient populations with long COVID or with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [&lt;span&gt;1&lt;/span&gt;]. In this study, IHHT was applied exclusively to patients with long COVID who had severely impaired functional capacity [&lt;span&gt;2&lt;/span&gt;]. The results showed that IHHT, as an additional treatment within a standardized inpatient rehabilitation program, was associated with improvements in functional capacity, health-related quality of life and both objective and subjective measures of symptom status. IHHT was demonstrated to be safe, well-tolerated and feasible within the context of an interdisciplinary rehabilitation program. Patients were allocated to the intervention group (receiving IHHT in addition to standard rehabilitation) or to the control group (receiving standard rehabilitation only) based on the clinical judgement of the attending physician. The two groups differed in some baseline characteristics.&lt;/p&gt;&lt;p&gt;Kulka and Tryba argue that these baseline differences suggest that the two groups may not represent the same patient population, potentially limiting the ability to draw conclusions regarding the treatment effect of IHHT. Contrary to this assumption, all patients in this single-centre study were enrolled by the same study team according to uniform inclusion criteria and following a prospectively defined study protocol. Only patients with a primary diagnosis of long COVID were included. While some baseline differences were observed (e.g., age, 6-min walk test [6MWT] distance, HDL levels and eGFR), the groups were similar in most clinical variables, including body composition, cardiovascular measures, respiratory capacity, concomitant medications for comorbidities and biochemical parameters. All patients were hospitalized in the same rehabilitation centre during the study and received the same standardized multidisciplinary rehabilitation program, which included physical rehabilitation (breathing exercises, endurance and strength training), relaxation techniques, education, occupational therapy, psychological counselling and optimized management of comorbidities. All patients received the same daily routines and dietary regimen. The only difference in treatment between groups was the addition of IHHT in the intervention group, administered according to a prospective treatment protocol as outlined in the study report. The statistical impact of this intervention was analysed using ANCOVA, assessing changes in functional capacity from baseline and adjusting for baseline measures. Thus, baseline differences were appropriately accounted for. This analysis revealed a significant benefit in the intervention group not only for t","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273527","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":"Delineating Life-Course Percentile Curves and Normative Values of Multi-Systemic Ageing Metrics in the United Kingdom, the United States, and China","authors":"Liming Zhang,&nbsp;Jiening Yu,&nbsp;Xueqing Jia,&nbsp;Zichang Su,&nbsp;Yingying Hu,&nbsp;Jingyun Zhang,&nbsp;Wei Yang,&nbsp;Xi Chen,&nbsp;Emiel O. Hoogendijk,&nbsp;Huiqian Huang,&nbsp;Zuyun Liu","doi":"10.1002/jcsm.13862","DOIUrl":"https://doi.org/10.1002/jcsm.13862","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;Ageing is a complex and multi-dimensional process that manifests heterogeneities across different organs/systems, individuals and countries. We aimed to delineate the life-course percentile curves and establish the normative values of multi-systemic (e.g., muscle-skeletal, brain, cardiovascular and pulmonary) ageing metrics for people under distinct sociodemographic contexts (i.e., sex, income and education).&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;Three national datasets, the UKB (the United Kingdom), the NHANES (the United States) and the CHARLS (China) were utilized for the analyses. We selected 14 ageing metrics (e.g., body mass index, grip strength, fat-free mass index, bone mineral content [BMC], bone mineral density [BMD], diastolic blood pressure, cognitive function and frailty index_Lab) that represent the functions of different organs/systems and plotted their sex-, educational- and income-specific percentile curves utilizing the GMALSS model. We also estimated the age-specific normative values for each ageing metric in distinct sociodemographic contexts.&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 functions of all metrics, except for cognitive function, manifested a progressive decline or maintained stability after adulthood (20s), especially after middle age (40s–50s). The cognitive function showed an evident decline in old age (70s–75s) (e.g., in the CHARLS: the median [IQR] cognitive function scores were 11.6 [9.1, 13.8], 10.3 [7.5, 12.9], 8.3 [5.5, 11.0] at the ages of 60, 70 and 80 for males, respectively). In the stratified analyses, males and females manifested disparities in percentile curves of ageing metrics involving the muscle-skeletal and cardiovascular systems. For instance, BMC and BMD manifested an evident decline after middle age in females, whereas they showed a slow decline after adulthood in males. Notably, we observed substantial income and educational disparities in percentile curves of several ageing metrics within Chinese participants: the ‘low-income’ and ‘low-education’ subgroups manifested an evident decline in ageing metrics (e.g., grip strength and frailty index_Lab) representative of multiple systems. By contrast, these income or educational disparities were not observed in the British and American participants.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our investigation delineated the potential heterogeneities and socioeconomic disparities in percentile curves of multi-systemic ageing metrics and provided their age-specific normative values tailore","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273263","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":"Reduction in Acetylation of Superoxide Dismutase 2 in Skeletal Muscle Improves Exercise Capacity in Mice With Heart Failure","authors":"Tomoka Masunaga,&nbsp;Tomoyasu Suenaga,&nbsp;Shouji Matsushima,&nbsp;Toru Hashimoto,&nbsp;Shingo Takada,&nbsp;Eri Noda,&nbsp;Yoshizuki Fumoto,&nbsp;Soichiro Hata,&nbsp;Takashi Yokota,&nbsp;Shintaro Kinugawa","doi":"10.1002/jcsm.13850","DOIUrl":"https://doi.org/10.1002/jcsm.13850","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;Skeletal muscle abnormalities, including mitochondrial dysfunction, play a crucial role in decreasing exercise capacity in patients with heart failure (HF). Although enhanced reactive oxygen species (ROS) production in skeletal muscle mitochondria has been implicated in skeletal muscle abnormalities, the underlying mechanisms have not been fully elucidated to date. Superoxide dismutase 2 (SOD2), an antioxidant enzyme present in mitochondria, is modified by acetylation, which reduces its activity. The aim of this study was to clarify whether reducing SOD2 acetylation by sirtuins 3 (SIRT3) activation improves skeletal muscle mitochondrial function and exercise capacity in HF model mice.&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;Myocardial infarction (MI) by ligation of the coronary artery or sham surgery was performed in male C57BL/6 J mice. Two weeks after surgery, these mice were treated with either the SIRT3 activator Honokiol (5 mg/kg body weight/day, i.p.) or vehicle. After 2 weeks of treatment, exercise capacity was evaluated by the treadmill test. Gastrocnemius muscle samples collected from the mice were used to measure mitochondrial function, as well as the levels of SIRT3, acetylated SOD2, and ROS production. Finally, the effect of adeno-associated virus serotype 9 (AAV9)-mediated overexpression of SIRT3 in the skeletal muscle on the exercise capacity of MI mice was investigated.&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;MI mice showed decreased cardiac function and skeletal muscle weight, but Honokiol did not affect these. Exercise capacity was significantly decreased in MI mice compared with sham mice by 24.9%, and Honokiol treatment improved the exercise capacity of MI mice by 40.4% (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The mitochondrial oxygen consumption rate was impaired in MI mice, but was improved by Honokiol treatment. SIRT3 expression was decreased by 26.8%, and SOD2 acetylation was increased by 36.9% in the skeletal muscle of MI mice compared with sham (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), and Honokiol treatment resulted in complete recovery of these levels (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Consistent with SOD2 acetylation, ROS production in the skeletal muscle was increased in MI mice and was ameliorated by Honokiol (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). SIRT3 expression was increased in MI + AAV9-SIRT3 mice compared with MI + AAV9-Control mice. The overexpression of SIRT3 improved exercise capacity without altering cardiac function.&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 SIRT3 activator Honokiol improved exercise capacity in M","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 3","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273062","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}