Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Influence of Resistance Training Variables to Improve Muscle Mass Outcomes in Sarcopenia: A Systematic Review With Meta-Regressions","authors":"Leo Delaire, Aymeric Courtay-Breuil, Joannès Humblot, Hubert Vidal, Marc Bonnefoy, Emmanuelle Meugnier","doi":"10.1002/jcsm.70162","DOIUrl":"10.1002/jcsm.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Resistance training (RT) is the first-line treatment to improve sarcopenia features. However, increasing muscle mass with RT remains challenging and displays inconsistent results. Manipulating training variables may present a novel approach to improve muscle mass gain in sarcopenic individuals. The present study aimed to measure the effectiveness of RT alone on muscle mass outcomes in older adults with sarcopenia and determine the influence of RT variables on muscle mass improvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We conducted a systematic review according to PRISMA standards to gather studies that conducted a supervised RT without nutritional intervention in sarcopenia-diagnosed older adults with a muscle mass outcome versus a control group. A search strategy was performed on PubMed, Medline, Cochrane and Google Scholar in the last 14 years, from the publication of the first agreement on the diagnosis (EWGSOP, 2010). Along with sample characteristics, we extracted and analysed the following training variables: frequency (number of sessions per week), intensity (in rating perceived effort and in % of the one repetition maximal load), duration (weeks), volume (number of sets per week), periodization (yes/no) and muscle failure (yes/no). First, we standardized the outcome with Hedge's <i>g</i> and pooled the effect size (ES) of each study in a univariate meta-analysis adjusted for risk of bias. Then, we performed training composition comparisons between ‘effective interventions’ and ‘ineffective interventions’, which were previously classified based on the 95% confidence interval (CI) effect size. Finally, relevant variables were regressed as moderators of the weighted ES in a mixed-effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 14 studies representing 528 individuals (73.1 ± 6.6 years, 385 women [73%] and 143 men [27%]) were included for analysis. A significant effect of RT to improve muscle mass was found with a small weighted ES estimate (<i>g</i> = 0.38 [0.18; 0.58] 95% CI, <i>p</i> ≤ 0.001). There was no publication bias across studies (<i>p</i> = 0.7). ‘Ineffective interventions’ included significantly older individuals (<i>p</i> ≤ 0.01). Training composition was homogenous between the groups. The final model showed that age was the only significant moderator of the ES (estimate = −0.06 [−0.08; −0.03] 95% CI, <i>p</i> ≤ 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In sarcopenic older adults, designing an evidence-based RT induces significant gains in musc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710802","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":"Ketogenic Nutrition in Combination With PPARα Activation Induced Metabolic Failure and Exacerbated Muscle Weakness in Septic Mice","authors":"Caroline Lauwers, Wouter Vankrunkelsven, Sarah Derde, Sarah Vander Perre, Inge Derese, Lies Pauwels, Ilse Vanhorebeek, Louis Libbrecht, Pieter Vermeersch, Jan Gunst, Greet Van den Berghe, Michael P. Casaer, Lies Langouche","doi":"10.1002/jcsm.70156","DOIUrl":"10.1002/jcsm.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Suppression of the peroxisome proliferator-activated receptor alpha (PPARα) has been related to poor outcomes in sepsis and may compromise ketogenesis during critical illness. Infusion of 3-hydroxybutyrate (3HB) was shown to attenuate muscle weakness in septic mice. We hypothesise that endogenous ketogenesis induced by pharmacological PPARα activation, either alone or combined with ketogenic nutrition, is safe and can also mitigate muscle weakness in septic mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we first (Study 1) assessed the safety and effectiveness (impact on ketosis and muscle weakness) of the PPARα agonist pemafibrate (1 mg/kg/d, <i>n</i> = 16), versus placebo (<i>n</i> = 15) combined with standard balanced parenteral nutrition (PN), composed of glucose, amino acids and long-chain triglycerides (LCT) (balanced-TPN). We subsequently (Study 2) evaluated the impact of pemafibrate combined with four types of PN on ketosis and muscle weakness: balanced-TPN (<i>n</i> = 18), TPN with extra LCTs (TPN + LCT, n = 18), low-dose pure LCT emulsion (Low-LCT, <i>n</i> = 16) and high-dose pure LCT emulsion (High-LCT <i>n</i> = 18). Carbohydrates and amino acids were omitted in the pure LCT groups. Healthy control mice (HC, <i>n</i> = 19) served as controls. Ex vivo muscle force was measured as the primary outcome. Metabolic, inflammatory and microstructural parameters were assessed on plasma and in muscle and liver tissue by targeted metabolomics, gene expression analysis, biochemical and metabolite assays and histological assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pemafibrate treatment with balanced-TPN upregulated hepatic gene expression of PPARα (<i>Ppara</i>) and its downstream genes (<i>Cd36</i>, <i>Cpt1a</i>, <i>Atgl</i>, <i>Acadl, Hadha, Acox1,</i> and <i>Hmgcs2</i>) (<i>p</i> < 0.0001) and was well tolerated. However, pemafibrate treatment with the use of balanced-TPN administration did not induce detectable ketosis or improve muscle weakness. In combination with pemafibrate, TPN + LCT also did not induce ketosis, nor did it affect muscle weakness. In contrast, 3-hydroxybutyrate plasma concentrations increased with High-LCT (95-fold) and Low-LCT (10-fold) (<i>p</i> < 0.0001) in combination with pemafibrate, yet muscle force declined further (High-LCT 25.0%, Low-LCT 10.7% of HC, <i>p</i> < 0.0001). Blood glucose was lowered with pure High-LCT and Low-LCT (High-LCT 86.9%, Low-LCT 55.1% of TPN, <i>p</i> < 0.05), while plasma lipids and LC-carnitines were increased (<i>p</i> < 0.0001). Markers of h","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710804","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":"Adipose–Muscle Crosstalk in COPD Cachexia: Early Adipose Atrophy Drives Subsequent Muscle Wasting","authors":"Takashi Shimada, Shotaro Chubachi, Keisuke Nishikawa, Tetsuya Arai, Hideto Iizuka, Shiro Otake, Kaori Sakurai, Junko Hamamoto, Mamoru Sasaki, Tomoki Maetani, Naoya Tanabe, Katsunori Masaki, Hiroki Kabata, Jun Miyata, Yoshitake Yamada, Masahiro Jinzaki, Hidetoshi Nakamura, Koichiro Asano, Koichi Fukunaga","doi":"10.1002/jcsm.70154","DOIUrl":"10.1002/jcsm.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD) is frequently associated with cachexia, leading to poor prognoses and reduced quality of life. However, the mechanisms underlying adipose tissue atrophy, its pathological significance and its interaction with skeletal muscle remain poorly understood. We hypothesised that adipose tissue atrophy precedes muscle wasting in COPD-associated cachexia, and muscle atrophy progresses through adipose–muscle crosstalk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed chest computed tomography scans of 185 patients with COPD to quantify the cross-sectional areas of the pectoralis muscle (PM), subcutaneous adipose tissue (SAT) and epicardial adipose tissue (EAT), and the percentage of low attenuation area (LAA%) as an index of emphysema. To elucidate the pathophysiological mechanisms underlying cachexia in COPD, we performed histological and molecular analyses of the lung, muscle and adipose tissues over time in a cigarette smoke–induced emphysema mouse model. Further, we used an in vitro culture system of differentiated adipocytes (3T3-L1) and myotubes (C2C12) to study the effects of cigarette smoke extract (CSE) on adipose–muscle interaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In patients with COPD, the areas of PM, SAT and EAT all demonstrated significant negative correlations with LAA%; notably, PM and EAT were independently associated with the extent of emphysematous changes. In the smoke-exposed murine model, adipose tissue atrophy was observed after 1 month of exposure, accompanied by increased expressions of IL-6 and IL-1β, macrophage infiltration and the upregulation of the lipolytic enzymes ATGL and HSL. The adipose atrophy had further progressed after 3 months of exposure, and the high expression of UCP1 was sustained, which suggested the browning of adipose tissue. Conversely, muscle atrophy was not evident at 1 month but became apparent after 3 months, coinciding with emphysema development. This was associated with the downregulation of the myogenic markers MyoD and Myogenin and the upregulation of the muscle degradation marker Atrogin-1. In vitro experiments revealed that CSE exposure reduced lipid droplet content and induced IL-6 and IL-1β expressions in adipocytes. Conditioned media from CSE-treated adipocytes triggered myotube atrophy and downregulated MyoD and Myogenin but upregulated Atrogin-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that cigarette smoke-induced adipose tissue atrophy precedes muscle wasting","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions","authors":"Stephan von Haehling,&nbsp;Ryosuke Sato,&nbsp;Henning Langer,&nbsp;Muhammad Shahzeb Khan,&nbsp;Andrew J. S. Coats,&nbsp;William Evans,&nbsp;Steven Heymsfield,&nbsp;Stefan D. Anker","doi":"10.1002/jcsm.70147","DOIUrl":"10.1002/jcsm.70147","url":null,"abstract":"<p>The Society on Cachexia and Wasting Disorders (SCWD) convened a Regulatory and Trial Update Workshop in Washington, D.C., in December 2024, assembling experts from academic institutions, the pharmaceutical industry and the US Food and Drug Administration (FDA) for focused discussions. This article summarizes the latter half of the meeting, which primarily focused on novel anti-obesity therapies based on incretin pathway alteration. Discussions highlighted the impact of glucagon-like peptide-1 (GLP-1) receptor agonists or GLP-1/glucose-dependent insulinotropic polypeptide (i.e., GLP-1/GIP) agonists on body composition and muscle health; the challenges of distinguishing ‘true’ skeletal muscle from fat-free tissue; the impact of treatment discontinuation and weight regain; advances in imaging and quantitative assessment of lean body mass; as well as insights from emerging muscle-preserving therapies (e.g., bimagrumab, pemvidutide and enobosarm). There are significant challenges in defining meaningful structural, functional and patient-reported endpoints for the use of muscle-‘protective’ drug therapies in the context of weight loss therapies. These also involve significant regulatory considerations for future drug development and approval pathways, for instance related to the very large number of individuals that may be considered for these therapeutic approaches as well as from the potential long (or life-long) duration of therapy considered with these drugs. Together, these discussions highlight the growing importance of integrating body composition and functional assessments in future clinical trials.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704149","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":"Thoracic Skeletal Muscle and Exercise Capacity in Adults With Congenital Heart Disease: A Cross-Sectional Imaging Analysis","authors":"Jacob D. Steffen,&nbsp;Seth Garton,&nbsp;Ravi Ashwath,&nbsp;Jennifer R. Maldonado,&nbsp;Krista Young,&nbsp;Colleen Lancial,&nbsp;Osamah Aldoss,&nbsp;Prashob Porayette","doi":"10.1002/jcsm.70157","DOIUrl":"10.1002/jcsm.70157","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The growing population of adults with congenital heart disease (ACHD) faces lifelong morbidities despite advancements in medical and surgical care. Sarcopenia, characterized by loss of muscle mass and strength, is linked to increased disability, poor quality of life and mortality. This study examines sex-specific thoracic skeletal muscle characteristics in ACHD patients using advanced imaging techniques, comparing them with healthy reference values and investigating their association with exercise capacity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Material and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this single-centre retrospective study, ACHD patients (age 18–50 years) who underwent both cardiopulmonary exercise tests and thoracic CT/MRI within a year were included. Skeletal muscle area (SMA) was manually measured and compared with healthy reference data.&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;Among 60 ACHD patients (mean age 28.3 ± 8.3 years; 48% females), males exhibited significantly lower SMA (T10: 116.8 ± 24.6 cm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; T11: 114.4 ± 24.7 cm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.0002) and skeletal muscle index (SMI) (T10: 37.2 ± 8 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.005; T11: 36.4 ± 8.1 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.0014) at T10 and T11 vertebral level, whereas females showed a reduction in SMA at T10 (79.7 ± 14.9 cm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.0242) and T12 (74.2 ± 10.7 cm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.0015) compared with healthy individuals. Females had significantly lower skeletal muscle radiation attenuation (SMRA) at T10 (16.3 ± 14.6 HU, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), T11 (17.1 ± 10.3 HU, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and T12 (25 ± 10.7 HU, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) levels, suggesting increased muscle fat content. Peak O&lt;sub&gt;2&lt;/sub&gt; pulse correlated with SMA at T10 (&lt;i&gt;r&lt;/i&gt; = 0.57, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.32, &lt;i&gt;p&lt;/i&gt; ≤ 0.0001), T11 (&lt;i&gt;r&lt;/i&gt; = 0.61, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.38, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and T12 (&lt;i&gt;r&lt;/i&gt; = 0.73, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.53, &lt;i&gt;p&lt;/i&gt; = 0.001) levels. Similar correlations were observed between peak O&lt;sub&gt;2&lt;/sub&gt; pulse and SMI, whereas peak VO&lt;sub&gt;2&lt;/sub&gt; correlated with SMA at T10 (&lt;i&gt;r&lt;/i&gt; = 0.27, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.07, &lt;i&gt;p&lt;/i&gt; = 0.0394) and T11 (&lt;i&gt;r&lt;/i&gt; = 0.34, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.11, &lt;i&gt;p&lt;/i&gt; = 0.02) and SMRA across all levels (T10: &lt;i&gt;r&lt;/i&gt; = 0.64, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.41, &lt;i&gt;p&lt;/i&gt; = 0.0076; T11: &lt;i&gt;r&lt;/i&gt; = 0.85, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.72, &lt;i&gt;p&lt;/i&gt; = 0.0003; T12: &lt;i&gt;r&lt;/i&gt; = 0.62, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.38, &lt;i&gt;p&lt;/i&gt; = 0.0327). SMA at T11 had a negative correlation with VE/VCO&lt;sub&gt;2&lt;/sub&gt; (&lt;i&gt;r&lt;/i&gt; = −0.36, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.13, &lt;i&gt;p&lt;/i&gt; = 0.01). There was ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696621","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":"Frailty in Cancer: Why Bother and Ways Forward","authors":"Luka Cavka,&nbsp;Alessandro Laviano,&nbsp;Mitja Lainscak","doi":"10.1002/jcsm.70139","DOIUrl":"10.1002/jcsm.70139","url":null,"abstract":"&lt;p&gt;Every era of medicine faces unique challenges. Today, aging is at the forefront, with the global population over 65 years expected to rise from 9% in 2019 to 17% in 2050. With this demographic shift, we must address the specific limitations of older adults, particularly frailty [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Frailty lacks a universal definition but broadly reflects a progressive decline in physiological and psychosocial reserves, resulting in vulnerability to stressors. The same insult—such as chemotherapy, infection or acute cardiopulmonary disease—may have very different outcomes in robust versus frail individuals [&lt;span&gt;2-5&lt;/span&gt;]. Reported prevalence varies widely due to inconsistent definitions, but studies suggest 11%–53% of elderly people are frail; the prevalence is higher in institutionalized elderly [&lt;span&gt;2&lt;/span&gt;]. Cancer is also largely a disease of older adults: About 30% of new diagnoses occur in those aged 65–74 and 25% in those over 75 [&lt;span&gt;6&lt;/span&gt;]. Some years ago, diagnosis of advanced cancer generally labelled patients with incurable disease; thus, work-up beyond malignancy was considered irrelevant. However, over time, effective therapies emerged that transformed many types of cancer into chronic diseases. These therapies are not without side effects which are tolerated differently depending on the patient's general condition. We should avoid futile treatments in fragile patients where adverse effects are likely to outweigh potential benefits. With a lack of guidelines or expert consensus, these decisions are largely based on ad hoc individual clinical judgement.&lt;/p&gt;&lt;p&gt;Within this new framework of cancer management, comorbidities affecting the quality of life and physical performance are relevant [&lt;span&gt;7, 8&lt;/span&gt;]. Physical performance and nutritional status-related assessments are gaining traction while frailty still remains underrecognized. The standard tools like ‘Fried frailty phenotype’ (FFP) and ‘Comprehensive Geriatric Assessment’ (CGA) are time-consuming and poorly suited to routine oncology practice.&lt;/p&gt;&lt;p&gt;Regarding open considerations about frailty in cancer patients, the work by Weinländer et al. [&lt;span&gt;9&lt;/span&gt;] in the recent issue of the Journal is spot on. The authors meticulously evaluated the concordance of the considered gold standard but more time-consuming tool FFP and clinically more convenient ‘Simple Frail Questionnaire’ (SFQ) [&lt;span&gt;10, 11&lt;/span&gt;]. FFP assesses five criteria (low physical activity, poor endurance, unintentional weight loss, weakness and slowness), categorizing patients as robust, prefrail or frail [&lt;span&gt;10&lt;/span&gt;]. SFQ uses a similar three-level classification but is quick, requires no special training and can be administered remotely. Weinländer et al. found a strong correlation between both scores (&lt;i&gt;r&lt;/i&gt;s = 0.65, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) with good internal consistency (Cronbach's alpha coefficient 0.80). Evaluation by SFQ and FFP revealed that 41% and 31% of advanced cancer patients","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704150","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":"Sarcopenic Obesity and Longitudinal Trajectories on Cognitive Performance and Subtle Cognitive Impairment Over 6 Years in Older Adults","authors":"Héctor Vázquez-Lorente,&nbsp;Indira Paz-Graniel,&nbsp;Hernando J. Margara-Escudero,&nbsp;Miguel Ángel Martínez-González,&nbsp;Dora Romaguera,&nbsp;D. Martinez Urbistondo,&nbsp;Ramon Estruch,&nbsp;Vicente Martín Sánchez,&nbsp;Josep Vidal,&nbsp;Montserrat Fitó,&nbsp;Nuria Goñi,&nbsp;Alice Chaplin,&nbsp;M. Angeles Zulet,&nbsp;Emilio Sacanella,&nbsp;José Antonio de Paz Fernández,&nbsp;Andreu Altés,&nbsp;Jesús F. García-Gavilán,&nbsp;Jadwiga Konieczna,&nbsp;J. Alfredo Martínez,&nbsp;Jordi Salas-Salvadó","doi":"10.1002/jcsm.70158","DOIUrl":"10.1002/jcsm.70158","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;Sarcopenic obesity has been suggested as a potential risk factor for cognitive decline; however, few prospective studies have been conducted to test this hypothesis. We aimed to assess the relationship between baseline sarcopenic obesity and 6-year trajectories of cognitive performance and subtle cognitive impairment in older adults.&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;This longitudinal study comprised 1097 older adults aged 55–75 years (mean [SD] age, 65.3 [4.9] years; 506 females [46.1%] and 591 males [53.9%]) exhibiting baseline overweight/obesity and metabolic syndrome. Baseline lower-limb muscle strength was determined by the validated 30-s Chair Stand Test. Baseline total body weight, fat mass percentage and appendicular lean mass were obtained through dual-energy x-ray absorptiometry scans. Baseline sarcopenic obesity (&lt;i&gt;n&lt;/i&gt; = 364 [33.2%]) was subsequently defined based on the new European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity consensus criteria. Cognitive performance was assessed at baseline, 2, 4 and 6 years of follow-up through five composite scores derived from a comprehensive battery of eight validated neuropsychological tests, encompassing global cognitive function, general cognitive function, executive function, attention and language. Subtle cognitive impairment was defined for those &lt;i&gt;z&lt;/i&gt;-scores 0.5 standard deviations below the mean for each cognitive performance composite score at baseline. Linear and logistic two-level mixed models including lost to follow-up participants were fitted as main analyses. Complete case analyses were additionally performed.&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;After adjusting for multiple covariates, main analyses showed that, compared to older adults without sarcopenic obesity, those with sarcopenic obesity showed a higher decline in global cognitive function (between-group difference, −1.0 [95% CI, −2.2 to 0.2] after 6 years; overall &lt;i&gt;p&lt;/i&gt; = 0.048) and general cognitive function (between-group difference, −2.5 [95% CI, −4.4 to 0.5] after 6 years; overall &lt;i&gt;p&lt;/i&gt; = 0.028) and had a higher risk of subtle global cognitive function impairment (between-group difference, 2.3 [95% CI, 0.9 to 5.6] after 6 years; overall &lt;i&gt;p&lt;/i&gt; = 0.038) over 6 years of follow-up. Associations remained consistent in the complete case analysis and attenuated when comparing those participants with baseline sarcopenic obesity with those only presenting sarcopenia, obesity or overweight. Of note, participants with baseline sarcopenia or obesity, compared to the absence of these conditions, showed no","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704148","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":"Determination of Ultrasound Reference Values for Diagnosing Low Muscle Mass in Older Chinese Adults","authors":"Shumin Li,&nbsp;Keying Xu,&nbsp;Ange Wang,&nbsp;Chenfan Qin,&nbsp;Nan Hua,&nbsp;Xinrui Ling,&nbsp;Liqian Xu,&nbsp;Caihong He,&nbsp;Shixian Zhou,&nbsp;Jing Chen,&nbsp;Qin Zhang,&nbsp;Yunmei Yang","doi":"10.1002/jcsm.70155","DOIUrl":"10.1002/jcsm.70155","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;Ultrasound is a promising tool for diagnosing sarcopenia, yet standardized cut-off points and criteria are currently lacking. This study aimed to identify the optimal muscle sites and reference values for diagnosing low muscle mass in older Chinese adults using ultrasound, with dual-energy X-ray absorptiometry (DXA) as the reference standard, and to compare its diagnostic performance with bioelectrical impedance analysis (BIA).&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 included 1011 participants aged over 60 years. Fat thickness (FT), muscle thickness (MT) and muscle cross-section area (CSA) at various sites, including biceps brachii, rectus abdominis, rectus femoris, vastus intermedius, vastus lateralis, vastus medialis and tibialis anterior, were assessed for participants. DXA measurements were used as the standard for defining low muscle mass. Receiver operating characteristic (ROC) curve analysis and 10-fold cross-validation were conducted to evaluate the prediction performance of ultrasound parameters for low muscle mass. The Youden index was employed to determine optimal cut-offs, while sensitivity, specificity and accuracy were calculated to assess diagnostic performance. Intra-class correlation coefficients (ICC) were used to evaluate inter-rater reliability between two examiners.&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;In males, the biceps brachii CSA (AUC = 0.832, 95% CI: 0.793–0.870) and in females, the tibialis anterior MT (0.833, 95% CI: 0.789–0.877) demonstrated superior predictive power for low muscle mass compared with other ultrasound parameters. A biceps brachii CSA &lt; 7.1 cm&lt;sup&gt;2&lt;/sup&gt; in males and tibialis anterior MT &lt; 2.3 cm in females were identified as effective indicators for diagnosing low muscle mass, with good sensitivities (73.9% in males, 73.6% in females), specificities (78.6% in males, 76.8% in females) and accuracies (75.7% in males, 75.8% in females). These values were comparable with those obtained using BIA (sensitivity: 62.6%, specificity: 80.2% and accuracy: 71.5%). Low muscle mass as defined by ultrasound was significantly associated with poor performance on the Short Physical Performance Battery, Activities of Daily Living and frailty indices, with effect sizes higher than DXA or BIA defined low muscle mass. The inter-rater reliability was excellent for biceps brachii CSA (ICC = 0.869, 95% CI: 0.650–0.937) and good for tibialis anterior MT (ICC = 0.730, 95% CI: 0.622–0.810).&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;Muscle ultrasound demonstra","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704146","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":"Slo1 Deficient Myoblast Exosomes-Derived miR-222-3p Inhibits Osteogenic Differentiation via Targeting of STAT3","authors":"Yonghui Wang,&nbsp;Xinrun Ma,&nbsp;Yang Chen,&nbsp;Chao Xia,&nbsp;Xue Lei,&nbsp;Junran Liu,&nbsp;Yunyi Jiang,&nbsp;Rang Xu,&nbsp;Yanhong Gao","doi":"10.1002/jcsm.70115","DOIUrl":"10.1002/jcsm.70115","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;Previous research has shown that the conditional knockout of Slo1 in muscle leads to a reduction in muscle strength and inhibits myogenic differentiation. Exosomes are emerging as necessary mediators of the crosstalk between muscle and bones. The present study focused on the communication between muscle and bone to investigate the effects and mechanisms of skeletal muscle-specific knockout of Slo1 on bone mass and bone metabolism.&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;Myf5-Cre mice were mated with Slo1&lt;sup&gt;flox/flox&lt;/sup&gt; mice to construct skeletal muscle-specific Slo1 knockout mice (CKO mice). The legs of the Slo1 CKO mice were isolated, and a series of examinations were conducted to monitor bone mineral density (BMD) and bone microstructure. Exosomes were extracted from C2C12-shNC and C2C12-shSlo1 cells and subjected to transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting (WB). The osteogenic effect of EXO-shSlo1 was examined in vitro and in vivo by Alkaline phosphatase (ALP) staining, q-PCR, WB and microCT. RNA sequencing (RNA-seq) analysis of EXO-shNC and EXO-shSlo1 was used to identify differentially expressed microRNAs. Mimics and inhibitors of miR-222-3p were transfected into MC3T3-E1 cells to induce differentiation. The predicted targets of miR-222-3p were examined with Luciferase, qPCR, and WB.&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;In Slo1 CKO mice, the bone mass decreased, and the microstructure was disrupted. TEM, NTA and WB assays showed that Slo1-silenced C2C12 cells secreted exosomes and localized to MC3T3-E1 cells and bone tissue through the circulation. EXO-shSlo1 inhibited osteogenesis both in vivo and in vitro, as demonstrated by the decreased ALP activity (~40%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), osteogenic marker expression (~30%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), mineral deposition in osteoblasts and BMD. qPCR was performed to confirm the exosome RNA-seq results, which indicated that miR-222-3p was increased by three times in the EXO-shSlo1 group compared with the EXO-shNC group. Transfection of mimics or inhibitors of miR-222-3p in MC3T3-E1 cells inhibited or improved osteogenic differentiation. Luciferase reporter assays revealed that miR-222-3p targets STAT3. The mRNA and protein level of STAT3 was affected by miR-222-3p. Through inhibiting miR-222-3p or upregulating STAT3, the EXO-shSlo1-mediated osteogenic inhibition of MC3T3-E1 cells was ameliorated, as indicated by increased ALP activity and osteogenic marker expression.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704147","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":"STIM1 Reduction Prevents Tubular Aggregate Formation and Compromises Muscle Performance in Ageing Mice","authors":"Laura Pérez-Guàrdia,&nbsp;Roberto Silva-Rojas,&nbsp;Jocelyn Laporte,&nbsp;Johann Böhm","doi":"10.1002/jcsm.70151","DOIUrl":"10.1002/jcsm.70151","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 an irreversible process involving the gradual decline of cellular functions in all tissues. In male mice, age-related loss of muscle force is accompanied by the formation of tubular aggregates, which are honeycomb-like structures composed of membrane tubules, proteins and Ca&lt;sup&gt;2+&lt;/sup&gt; deposits. Tubular aggregates are also found in tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two clinically overlapping human disorders affecting skeletal muscle, bones, skin, spleen and platelets. TAM/STRMK is caused by gain-of-function mutations in the ubiquitously expressed Ca&lt;sup&gt;2+&lt;/sup&gt; sensor STIM1 and results in excessive extracellular Ca&lt;sup&gt;2+&lt;/sup&gt; entry and the dysregulation of Ca&lt;sup&gt;2+&lt;/sup&gt; homeostasis.&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;To understand the correlation between ageing, tubular aggregate formation, Ca&lt;sup&gt;2+&lt;/sup&gt; and STIM1, we conducted comparative analyses of WT and &lt;i&gt;Stim1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/−&lt;/i&gt;&lt;/sup&gt; male mice until 18 months of age. We examined growth, general and specific muscle force, fatigability and muscle structure.&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;&lt;i&gt;Stim1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/−&lt;/i&gt;&lt;/sup&gt; mice were born with the expected Mendelian ratio and showed unremarkable postnatal development with normal body and organ weight. However, at 18 months, &lt;i&gt;Stim1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/−&lt;/i&gt;&lt;/sup&gt; mice manifested delayed muscle contraction (&lt;i&gt;Δ&lt;/i&gt; = 28%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and relaxation (&lt;i&gt;Δ&lt;/i&gt; = 40%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) kinetics as well as exacerbated fatigue (&lt;i&gt;Δ&lt;/i&gt; = 28%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) compared with age-matched controls. Morphological investigations of &lt;i&gt;Stim1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/−&lt;/i&gt;&lt;/sup&gt; muscle sections by light and electron microscopy uncovered a shift towards slow myofibres and mitochondrial proliferation accompanied by enhanced SDH activity (&lt;i&gt;Δ&lt;/i&gt; = 27%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), an almost twofold increase in ROS production (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), and signs of mitophagy—all representing histopathological hallmarks of age-related deterioration of muscle function known as sarcopenia. Strikingly, tubular aggregates—though abundant in WT muscles at 18 months—were absent in &lt;i&gt;Stim1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/−&lt;/i&gt;&lt;/sup&gt; mice.&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;Taken together, STIM1 depletion by 50% had no discernible effect on muscle function in young adult male mice, but compromised muscle performance and resistance to fatigue at later life stages. These findings highlight a critical role of STIM1 and Ca&lt;sup&gt;2+&lt;/sup&gt; balance in the maintenance of muscle phy","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 6","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696640","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}