Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"RAGE Re-Expressed at Myofibre Level Drives Muscle Wasting in Cancer Conditions.","authors":"Sara Chiappalupi, Giulia Gentili, Laura Salvadori, Martina Paiella, Marcello Manfredi, Vittoria Federica Borrini, Kaamashri Mangar, Ann Marie Schmidt, Maurizio Muscaritoli, Francesca Riuzzi, Guglielmo Sorci","doi":"10.1002/jcsm.70302","DOIUrl":"10.1002/jcsm.70302","url":null,"abstract":"<p><strong>Background: </strong>Cancer cachexia (CC) is a highly debilitating syndrome characterized by loss of body and muscle weight affecting most advanced cancer patients. The receptor for advanced glycation end-products (RAGE) is expressed by several cell types and sustains the inflammatory response in acute and chronic diseases. Total ablation of RAGE (Ager<sup>-/-</sup> mice) translates into restrained CC and increased survival in tumour-bearing mice. RAGE, which is not expressed in adult healthy myofibres, is re-expressed in atrophying myofibres in cancer conditions. However, the specific contribution of muscular RAGE to CC was unknown.</p><p><strong>Methods: </strong>Using an HSA/Cre-loxP system, we generated a tamoxifen-inducible conditional Ager<sup>mKO</sup> mouse model in which RAGE is selectively ablated in myofibres. Tamoxifen-treated Ager<sup>mKO</sup>, Ager<sup>flox</sup> and Ager<sup>-/-</sup> mice were subcutaneously injected with Lewis lung carcinoma (LLC) cells, and body changes and survival were monitored until 25 dpi, when histological, molecular and proteomic analyses were performed in tumour-bearing and control mice. Muscle samples of pre-cachectic and cachectic pancreatic cancer patients were analysed to validate the results.</p><p><strong>Results: </strong>Compared with LLC-Ager<sup>flox</sup> mice, LLC-Ager<sup>mKO</sup> mice showed reduced (7.5% [p = 0.004] vs. 15.1% [p < 0.0001]) body weight loss, no significant reduction of hind-limb muscle mass and strength and myofibre cross-sectional areas, increased survival (69.2% vs. 42.9% mice alive at 25 dpi) and restrained muscle and serum pro-inflammatory factors. Mechanistically, Ager<sup>mKO</sup> muscles resist cancer-induced atrophy by maintaining an active Akt-GSK-3β-PGC-1α pathway, and increasing the synthesis of myosin heavy chain (MyHC)-I and -IIa (71.8% [p = 0.008] and 73.9% [p = 0.002] increase, respectively) along with a 76.3% (p = 0.008) increase in hybrid MyHC-I/IIa myofibres. Distinct proteomic signatures characterize muscles of tumour-bearing mice in dependence on RAGE expression, supporting a protective effect of RAGE ablation in muscles. LLC/Ager<sup>mKO</sup> muscles showed increased amounts of several enzymes involved in glycolysis and glucose catabolism, typical of Warburg metabolism. Noteworthy, muscles of pre-cachectic and cachectic cancer patients showed ~3-fold increase (p < 0.05) in RAGE amounts and reduced Akt-GSK-3β-PGC-1α pathway, compared with healthy control subjects.</p><p><strong>Conclusions: </strong>Our data provide evidence that RAGE engagement at myofibre level drives loss of body and muscle weights and inflammation in cancer conditions. RAGE ablation in muscles confers resistance to CC through myofibre remodeling and glycolytic reprogramming. On the clinical side, the overexpression of RAGE is an early event in muscles of cancer patients, suggesting a role for RAGE in the onset of the cachectic syndrome. Thus, the molecular targeting of","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70302"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855771","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":"Not All Weight Loss Is Equal: Towards Muscle-Preserving Therapies in Obesity.","authors":"Joseph D Abraham,Muhammad Shahzeb Khan,Stefan D Anker","doi":"10.1002/jcsm.70298","DOIUrl":"https://doi.org/10.1002/jcsm.70298","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"4 1","pages":"e70298"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creatine/Creatinine Ratio and Myostatin as Biomarkers to Monitor Muscle Function in Duchenne Muscular Dystrophy Patients.","authors":"Chiara Degan, Roula Tsonaka, Sharon I de Vries, Nadine A Ikelaar, Menno van der Holst, Hermien E Kan, Erik H Niks, Pietro Spitali","doi":"10.1002/jcsm.70320","DOIUrl":"10.1002/jcsm.70320","url":null,"abstract":"<p><strong>Background: </strong>Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle wasting leading to early loss of motor function. Functional tests monitor disease progression and serve as clinical trial endpoints but are influenced by maturation in younger patients, high intra-patient variability and patient motivation. Clinical milestones, instead, have been used to identify modifiers of disease progression but are rarely used as primary endpoints since clinical trials are usually too short to capture them. Blood biomarkers, that can reflect disease progression and objectively evaluate treatment responses, offer a valuable alternative. In this study, we investigated whether longitudinal observations of biomarkers myostatin and creatine/creatinine ratio (Cr/Crn) are associated with functional tests, such as 6-min walk test, North Star Ambulatory Assessment (NSAA), 10-m walk-run test velocity (10MWT), Performance of Upper Limb (PUL2.0) and disease milestones like loss of ambulation, overhead reach and hand-to-mouth function.</p><p><strong>Methods: </strong>We used longitudinal data from an observational study on 74 DMD patients followed between 2009 and 2022 with annual visits to the LUMC outpatient clinic, linked to 408 serum samples. Associations between log2-biomarkers, functional tests and clinical milestones were assessed using linear mixed models and time-dependent Cox models. A post-hoc sample size calculation was performed to evaluate whether the biomarkers' lower intra-patient variability (NSAA SD: 0.79, 10MWT SD: 0.88, log2-myostatin and log2-Cr/Crn SDs: 0.57) may improve future clinical trials design.</p><p><strong>Results: </strong>Lower Cr/Crn and higher myostatin levels were associated with better functional performance and a less rapid decline in ambulation, given fixed treatment and BMI. Children with one-unit higher log2-myostatin levels had, on average, 4.73 points higher NSAA and 3.40 points higher PUL2.0 (p-values < 0.001) and were 42% less likely to lose ambulation over the following year. Conversely, children with one-unit lower log2-ratio levels had, on average, 11.40 points higher NSAA and 7.18 points higher PUL2.0 (p-values < 0.001) and were 3.67 times more likely to remain ambulant. We proved that incorporating log2-myostatin and log2-Cr/Crn as endpoints could reduce the required sample size for clinical trials by more than half without compromising statistical power. For instance, to detect a yearly drop of 3 points in the NSAA with 80% power, recruitment requires almost 80 participants in a 1:1 randomized trial, compared to a little more than 50 patients for the respective value of log2-myostatin or log2-Cr/Crn.</p><p><strong>Conclusions: </strong>These findings support the potential of myostatin and Cr/Crn as monitoring biomarkers to enhance trial design and endpoints in clinical and interventional trials for DMD.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70320"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256719","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 Health and Prognosis in Patients With Cancer: New Insights.","authors":"Emanuele Cereda, Amanda Casirati, Maria Cristina Gonzalez, Nilian Carla Souza, Carla M Prado, Katherine L Ford, Silvia Fernandes Mauricio, Maria Isabel Toulson Davisson Correia, Paolo Pedrazzoli, Riccardo Caccialanza","doi":"10.1002/jcsm.70292","DOIUrl":"10.1002/jcsm.70292","url":null,"abstract":"<p><strong>Background: </strong>Reduced muscle mass and impaired composition have each been independently associated with worse outcomes in patients with cancer. However, emerging evidence suggests that reduced muscle strength-namely, dynapenia-may be particularly important for prognostication, as it is easier to assess in clinical practice compared to muscle mass. Importantly, muscle mass and composition-as assessed with computed tomography images-may not fully capture key physiological changes and/or reflect whole-body alterations, particularly in patients who remain within the normal range. We investigated the predictive power for mortality of low muscle mass and impaired composition, weight loss (WL) and low strength, as well as their combination, in a cohort of patients with cancer.</p><p><strong>Methods: </strong>Baseline data on muscle mass and radiodensity (Hounsfield units [HU]) at the L3 level-assessed using computed tomography-along with 6-month unintentional WL (relevant if ≥ 10% of usual body weight) and muscle strength by handgrip were pooled for 477 patients with cancer (59.1% male, mean age 61.2 ± 12.8 years) from studies conducted in Brazil, Canada and Italy. Patients were categorized by sex and body mass index-specific cutoffs for low skeletal muscle mass index, low skeletal muscle radiodensity, WL ≥ 10% and low handgrip strength. Patients were followed for at least 12 months until death or censoring.</p><p><strong>Results: </strong>During a median follow-up of 43 months (IQR: 28-83), 188 patients died. Kaplan-Meier analysis showed no survival differences for low skeletal muscle index or low radiodensity, regardless of handgrip strength. Only WL ≥ 10% consistently identified patients with poorer prognosis, independently of low handgrip strength. Fully adjusted Cox's regression models showed an independent association only with WL (HR = 1.56 [95% CI: 1.12;2.16]; p = 0.008) and low handgrip strength (HR = 2.07 [95% CI: 1.47;2.92]; p < 0.001), as well as an increased risk for all low handgrip strength/%WL categories. Mortality risk increased across all low handgrip strength/%WL categories. Among the eight risk groups combining low skeletal muscle mass index, WL ≥ 10% and low handgrip strength, only those including WL ≥ 10% and low handgrip strength were significantly associated with higher mortality. Low skeletal muscle mass index contributed to a worse prognosis only when combined with both WL ≥ 10% and low handgrip strength. Similar results were observed when skeletal muscle radiodensity was used in replacement of skeletal muscle mass index.</p><p><strong>Conclusions: </strong>In patients with cancer, muscle strength and WL were stronger survival predictors than muscle mass and composition, reinforcing their relevancy as easily assessed key markers of muscle health.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70292"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758382","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":"Effects of Omega-3 Supplementation in Sarcopenia After Bariatric Surgery: A Triple-Blind Randomized Controlled Clinical Trial.","authors":"André Vicente Bigolin, Júlia Iaroseski, Randhall Bruce Carteri, Giovanna Severino Rodrigues, Rafaela de Andrade, Luiz Alberto De Carli, Elisa Loch Razzera, Izabele Vian, Roberta de Almeida da Silva, Antônio Nocchi Kalil, Luis Fernando Ferreira","doi":"10.1002/jcsm.70321","DOIUrl":"10.1002/jcsm.70321","url":null,"abstract":"<p><strong>Background: </strong>Bariatric surgery is an effective treatment for obesity but induces substantial muscle loss, potentially leading to sarcopenia. Omega-3 fatty acids have been associated with improved muscle metabolism, but their effect in the postoperative period of bariatric surgery remains unclear.</p><p><strong>Methods: </strong>A triple-blind randomized clinical trial following CONSORT guidelines. Patients undergoing bariatric surgery were randomly assigned to receive omega-3 supplementation (2000 mg/day of EPA + DHA) or placebo (sunflower oil) for 90 days, including 15 days preoperatively and 75 days postoperatively. Assessments were performed at baseline, 45 days and 105 days after the start of supplementation. Outcomes included skeletal muscle mass (bioelectrical impedance [BIA]), handgrip strength (HGS) and functional performance (timed up and go [TUG] test).</p><p><strong>Results: </strong>Fifty-eight patients were randomized (81% women; mean age 38.2 ± 9.9 years; mean body mass index [BMI]: 41.1 ± 4.6 kg/m²). At baseline, intervention and control groups were comparable in weight (112.7 ± 19.1 vs. 113.0 ± 17.9 kg; p = 0.946), muscle mass (33.5 ± 7.5 vs. 32.5 ± 7.3 kg; p = 0.603), HGS (33.3 ± 9.6 vs. 35.4 ± 10.2 kgf; p = 0.428) and TUG (8.7 ± 3.0 vs. 8.7 ± 1.8 s; p = 0.912). Between baseline and 105 days, muscle mass decreased significantly in both groups (-3.1 ± 0.3 kg; -2.2 ± 0.5 kg; both p < 0.001), without interaction between groups (p = 0.300). HGS remained stable (Δ -0.8 to +2.3 kgf; all p ≥ 0.364), and TUG performance did not change significantly (Δ 0.0-1.1 s; all p ≥ 0.106). Weight loss was marked in both groups (-19.3 ± 1.9 vs. -17.7 ± 2.1 kg; both p < 0.001). The incidence of gastrointestinal symptoms ≥ 3 times/week was similar (34.5% vs. 13.6% at 45 days; p = 0.114). No serious adverse events occurred.</p><p><strong>Conclusions: </strong>Omega-3 supplementation (2000 mg/day) during the perioperative period of bariatric surgery did not prevent muscle mass loss nor improve muscle strength or functional performance within 105 days of follow-up. Although the supplementation was safe and well tolerated, it did not demonstrate efficacy in mitigating early sarcopenia-related outcomes in this population.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT06494566.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70321"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13265123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248228","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 'Asian Reference Values for Handgrip Strength, Gait Speed, Five-Times-Sit-to-Stand Test, Muscle Mass and Calf Circumference' by Grgic et al.","authors":"Wee-Shiong Lim, Prasert Assantachai, Reshma Merchant, Chang Won Won, Jean Woo, Liang-Kung Chen, Hidenori Arai","doi":"10.1002/jcsm.70317","DOIUrl":"10.1002/jcsm.70317","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70317"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262193","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":"MyoRep: A Novel Reporter System to Detect Early Muscle Atrophy In Vitro and In Vivo.","authors":"Andrea D Re Cecconi, Nicoletta Rizzi, Mara Barone, Federica Palo, Martina Lunardi, Mara Forti, Adriana Maggi, Paolo Ciana, Giulia Terribile, Michela Chiappa, Lorena Zentilin, Rosanna Piccirillo","doi":"10.1002/jcsm.70296","DOIUrl":"10.1002/jcsm.70296","url":null,"abstract":"<p><strong>Background: </strong>Muscle atrophy occurs during physiological (i.e., fasting) and pathological conditions (i.e., cancer) and anticipates death. Since not all patients will undergo muscle wasting, it would be highly useful to identify them soon to intervene early. We aim to generate a reporter system to follow only pathological, but not physiological, muscle wasting through in vivo imaging.</p><p><strong>Methods: </strong>Comparing the upstream non-coding regions of a subset of atrophy-related genes or atrogenes, using the MuRF1 promoter as a backbone, we cloned various promoters upstream of Firefly Luciferase. The best hits selected in vitro were further compared in in vivo imaging if able to sense early atrophy induced by MCG101 sarcoma or sciatic nerve resection through plasmid electroporation or AAV9 injections. The best promoter was used to generate the reporter mouse MyoRep, expressing the cassette in all skeletal and cardiac muscles using the loxP system.</p><p><strong>Results: </strong>Luciferase assays showed that only the newly generated promoters of MuRF1, one containing glucocorticoid-responsive elements or GRE (TWIST) (p ≤ 0.01, 1.7 FC) and a GRE-less promoter (GREDEL) (p ≤ 0.0001, 1.6 FC), discriminated the supernatants from cachectic tumoural cells (C26) from non-cachectic ones (4T1). Comparing both reporters electroporated in leg muscles, we found that GREDEL, but not TWIST, anticipated atrophy by 6 days in MCG101 carriers (p ≤ 0.05) and by 8 days upon denervation (p ≤ 0.05), recapitulating MuRF1 inductions. TWIST, but not GREDEL, drove an undesirable bioluminescent signal in vitro to dexamethasone (p ≤ 0.001, 1.5 FC) and in vivo upon fasting (p = 0.0553, 3 FC). GREDEL-carrying AAV9 injected in the legs of Apc^Min/+ mice unraveled sex-different cachexia and anticipated body emaciation by 1 week (p ≤ 0.001, 3.7 FC). GREDEL was then used to generate the MyoRep mouse. Dorsal view of bioluminescent signal of MCG101-carrying MyoRep mice increased already 6 days from tumour injection (p ≤ 0.01, 1.7 FC) when tumour is still unpalpable. Denervated MyoRep mice emitted a signal already 1 day after surgery (p ≤ 0.05, 1.4 FC), anticipating atrophy. Male Apc^Min/+ mice display less musclin in their muscles (p ≤ 0.05, 0.4 FC) and plasma (p ≤ 0.01, 0.6 FC). Such mice, when expressing MyoRep in their muscle legs, were given the anti-catabolic myokine musclin. The emitted signal was decreased by 30% 3 weeks after musclin-AAV9 administration (p ≤ 0.05), supporting MyoRep useful to test anti-atrophic drugs.</p><p><strong>Conclusions: </strong>Since MyoRep detects only pathological atrophy anticipating wasting, it represents an unprecedented tool to predict it early in diseases with local or systemic atrophy. It could also be useful to identify early biomarkers of atrophy and new drugs at once.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70296"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925052","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":"Combined Bisoprolol and Megestrol Acetate Improves Survival and Preserves Cardiac Performance in a Rat Model of Cancer Cachexia.","authors":"Zihao Chen, Siqi Wang, Sandra Palus, Stefan D Anker, Wolfram Doehner, Jochen Springer","doi":"10.1002/jcsm.70313","DOIUrl":"10.1002/jcsm.70313","url":null,"abstract":"<p><strong>Background: </strong>Cancer cachexia is associated with rapid body wasting and cardiac dysfunction. Bisoprolol (BIS) and megestrol acetate (MA) improve selected cachexia phenotypes in the Yoshida AH-130 model, but their combined effects are not defined. We tested reduced-dose combined treatment of BIS and MA (COMB) on survival and organ-specific outcomes.</p><p><strong>Methods: </strong>Male Wistar Han rats (approx. 200 g) received intraperitoneal Yoshida AH-130 hepatoma cells and were treated with placebo (PL, n = 49), BIS (5 mg/kg/day, n = 23), MA (100 mg/kg/day, n = 10) or COMB (BIS 3.75 mg/kg/day + MA 75 mg/kg/day, n = 16). Outcomes included survival, echocardiography (baseline and Day 11), body composition (EchoMRI), terminal tissue weights, food intake and spontaneous locomotor activity.</p><p><strong>Results: </strong>COMB reduced mortality versus placebo (HR = 0.21, p < 0.0001) and had the lowest HR among treatment groups. BIS also reduced mortality versus PL (HR = 0.32, p = 0.0007), whereas MA did not reach statistical significance (HR = 0.49, p = 0.082). COMB did not differ significantly from BIS (HR for COMB vs. BIS = 0.48, p = 0.28) or MA (HR for COMB vs. MA = 0.23, p = 0.06). On Day 11, COMB showed higher LVEF than PL (64.1% ± 9.7% vs. 50.5% ± 12.8%, p < 0.01), higher LV stroke volume (186 ± 49 μL vs. 112 ± 55 μL, p < 0.001) and higher LV mass (515 ± 95 mg vs. 429 ± 65 mg, p < 0.01); changes from baseline were smaller in COMB than PL for LVEF (Δ -12.0% ± 8.9% vs. -24.3% ± 16.2%, p < 0.05) and LV mass (Δ -57 ± 93 mg vs. -137 ± 79 mg, p < 0.05). Body weight, fat mass and lean mass decreased in all groups; COMB showed smaller reductions than PL (p < 0.05) but did not differ from BIS or MA (p > 0.05). BAT weight was higher in COMB than PL (p < 0.001) and higher than BIS (p < 0.001). Food intake on Day 11 was higher than PL in all active groups, and locomotor activity was higher than PL in MA and COMB.</p><p><strong>Conclusions: </strong>COMB reduced mortality versus placebo and showed the lowest HR among treatment groups, accompanied by preserved cardiac performance and a distinct BAT response. Differences versus monotherapy were not statistically significant. Future studies should test optimized dosing and include exposure assessment and tissue profiling to determine benefit over monotherapy and to clarify the basis of the cardiac and BAT phenotypes.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70313"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004010","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":"Gut Microbiota-Linked Benefits of Low-Intensity Pulsed Ultrasound Rejuvenate the Ageing Muscle.","authors":"Jia-Hua Jhuang,Kuo-Cheng Lan,Ting-Yu Chang,Ding-Cheng Chan,Shing-Hwa Liu","doi":"10.1002/jcsm.70291","DOIUrl":"https://doi.org/10.1002/jcsm.70291","url":null,"abstract":"BACKGROUNDAgeing is an inevitable biological process that contributes to increased prevalence of age-associated diseases, including sarcopenia, defined by progressive loss of muscle mass, functional decline and a heightened risk of injury. Developing effective interventions remains a critical clinical priority. This study employed a natural ageing mouse model to investigate whether noninvasive low-intensity pulsed ultrasound (LIPUS), a therapeutic ultrasound, delivered to the abdomen, could alleviate age-related muscle deterioration and whether its effects were linked to gut microbiota modulation.METHODSC57BL/6 mice were maintained until 92 weeks of age, after which abdominal LIPUS stimulation was administered for 8 weeks. At 100 weeks, both forelimb and hind limb grip strength were assessed prior to euthanasia. Faecal samples from the distal colon were collected for microbiota profiling, and gastrocnemius muscles were harvested for downstream analyses.RESULTSNaturally aged mice exhibited sarcopenia-like characteristics, including impaired muscle performance, reduced myofiber diameter and decreased muscle weight (n = 6, p < 0.01, p < 0.001). Age-related renal impairment promoted the accumulation of advanced glycation end products (AGEs) in skeletal muscle, triggering pro-inflammatory signalling cascades characterized by elevated COX-2, phosphorylated NF-κB, NLRP3, IL-1β and Caspase-1 (n = 5-6, p < 0.01). LIPUS treatment significantly improved muscle strength (forelimb and hind limb grip strength, n = 6, p < 0.001, p < 0.01) and muscle mass (n = 6, p < 0.01), while suppressing inflammatory mediators (n = 5-6, p < 0.05). Gut microbiota analysis showed that LIPUS increased microbial diversity (n = 5-6, p < 0.05) and altered taxonomic composition, enriching anti-inflammatory taxa such as Lactobacillus, Bifidobacterium, Faecalibaculum and Coriobacteriaceae_UCG_002 (n = 6, p < 0.05). Correlation analysis indicated that these LIPUS-enriched taxa were positively associated with enhanced muscle performance. These data suggest that LIPUS mitigates sarcopenia in naturally aged mice by restoring muscle integrity and attenuating inflammation, possibly via gut microbiota regulation.CONCLUSIONSThis study shows that natural ageing in mice induces sarcopenia-like features with inflammatory activation and gut microbiota alterations. Abdominal LIPUS treatment alleviated muscle loss, reduced inflammation and promoted beneficial microbes, rejuvenating the ageing muscle. These findings highlight LIPUS as a safe, noninvasive and potentially translatable strategy for sarcopenia, warranting further investigation of its microbiota-muscle interactions.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"73 1","pages":"e70291"},"PeriodicalIF":8.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triglyceride-Glucose-Waist-to-Weight Index: Novel Biomarker for Mild Cognitive Impairment in Older People With Sarcopenic Obesity.","authors":"Yue Xing, Qian Liu, Xiangfeng He, Lin Ma, Yanping Song, Nan Chen PhD","doi":"10.1002/jcsm.70307","DOIUrl":"10.1002/jcsm.70307","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenic obesity (SO) is closely associated with mild cognitive impairment (MCI). However, traditional body composition-based diagnostic criteria for SO fail to adequately incorporate insulin resistance, a key pathophysiological mechanism. This study aimed to investigate the association between SO, defined using multiple diagnostic criteria including novel insulin resistance indices, and MCI and to identify the optimal SO criterion for MCI identification.</p><p><strong>Methods: </strong>This study analysed data from the 2025 Chongming Older People Screening Project, CHARLS (2015-2020) and ELSA (2012-2017). We used multivariable logistic regression to assess the link between SO and MCI. The optimal obesity indicator for identifying MCI in sarcopenia was identified using ROC analysis and then incorporated into an XGBoost model to detect MCI risk. Subgroup analyses were performed to assess the association between SO and decline in multiple cognitive domains.</p><p><strong>Results: </strong>This study included 2326 individuals from the 2025 Chongming Older People Screening Project, 3392 from CHARLS and 1825 from ELSA. The mean age was 72.62 ± 5.56 years in the cross-sectional study, 66.70 ± 5.39 years in CHARLS and 67.99 ± 5.55 years in ELSA. The proportion of female participants was 55.93% in the cross-sectional study, 57.59% in ELSA and 40.60% in CHARLS. MCI was consistently identified across all assessment tools in three independent cohorts using the metabolically oriented definition integrating sarcopenia with an elevated triglyceride-glucose-waist-to-weight index (TyG-WWI) (Chongming: OR = 3.04, 95% CI: 1.83-5.07, p < 0.001; CHARLS: HR = 1.57, 95% CI: 1.01-2.42, p = 0.043; and ELSA: HR = 1.87, 95% CI: 1.01-3.46, p = 0.047). TyG-WWI was identified as the optimal obesity indicator to identify MCI (AUC = 0.71, 95% CI: 0.63-0.78). The machine learning model based on TyG-WWI demonstrated strong discriminative performance in the cross-sectional study (AUC = 0.93, 95% CI: 0.90-0.97) and maintained robust discriminative ability in external validation (CHARLS: AUC = 0.86, 95% CI: 0.80-0.92; ELSA: AUC = 0.84, 95% CI: 0.73-0.95). Subgroup analyses revealed that SO was associated with decline in multiple cognitive domains, particularly executive function and memory.</p><p><strong>Conclusions: </strong>This study demonstrates that a metabolically oriented SO definition integrating sarcopenia with elevated TyG-WWI is a more effective tool for identifying MCI among community-dwelling older people compared with traditional body composition-based criteria.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 3","pages":"e70307"},"PeriodicalIF":9.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872520","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}