Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Longitudinal association between statins and changes in CT-derived body composition in patients with abdominal aortic aneurysm","authors":"Nicholas A. Bradley, Amy Walter, Chiara Sankey, Alasdair Wilson, Tamim Siddiqui, Campbell S.D. Roxburgh, Donald C. McMillan, Graeme J.K. Guthrie","doi":"10.1002/jcsm.13565","DOIUrl":"https://doi.org/10.1002/jcsm.13565","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Loss of skeletal muscle mass and systemic inflammation may offer prognostic value in patients with abdominal aortic aneurysm (AAA). The longitudinal progression of abnormal body composition parameters and their determinants is poorly reported. Statins are widely used medications that improve the prognosis of cardiovascular disease and interact with both muscle tissue and systemic inflammation. The present study aimed to describe the association between statin therapy and both pre-operative and longitudinal CT-derived body composition in patients undergoing elective intervention for AAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 756 consecutive patients undergoing elective intervention for AAA at three centres were retrospectively recruited. Body composition analysis was performed on pre-operative and follow-up CTs at L3 to generate subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index and density (SMI and SMD). Systemic inflammation was assessed using the systemic inflammatory grade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 756 patients (702 [93%] males, median [interquartile range, IQR] age 73.0 [11.0] years) were included, with a median (IQR) follow-up of 67.0 (32) months and 235 deaths during the follow-up period. There were 582 patients (77%) receiving statin therapy and 174 patients (23%) not receiving statin therapy. Follow-up CTs were available for 273 patients. From pre-operative to follow-up CTs, there was a decrease in median SMI (<i>P</i> < 0.001) and SMD (<i>P</i> < 0.001) and an increase in the comparative prevalences of low SMI (43% vs. 50%, <i>P</i> < 0.01) and low SMD (64% vs. 88%, <i>P</i> < 0.001). There were no differences in baseline clinicopathological characteristics, systemic inflammation or pre-operative CT-derived body composition parameters between patients with and without >10% loss of skeletal muscle mass. In patients with ≤10% loss of SMI, mean (95% confidence interval) survival was 91.6 (87.2–95.9) months versus 89.3 (80.4–98.2) months in patients with >10% loss of SMI (<i>P</i> = 0.58). Patients receiving statin therapy had a higher American Society of Anesthesiologists grade (<i>P</i> < 0.001), a higher body mass index (BMI) (<i>P</i> < 0.05) and a greater prevalence of normal pre-operative SMI (<i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with AAA, skeletal muscle mass and density appear to progressively decline despite treatment of AAA, though specific det","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809508","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":"Activating Striatal Parvalbumin Interneurons to Alleviate Chemotherapy-Induced Muscle Atrophy","authors":"Jun Hu, Jingyuan Liu, Yuqing Yan, Ziyu Shen, Junlong Sun, Yongjun Zheng","doi":"10.1002/jcsm.13782","DOIUrl":"https://doi.org/10.1002/jcsm.13782","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cisplatin is a widely used chemotherapeutic agent for treating solid tumours. Still, it induces severe side effects, including muscle atrophy. Understanding the mechanisms of cisplatin-induced muscle loss and exploring potential therapeutic strategies are essential. Parvalbumin (PV) interneurons in the striatum play a crucial role in motor control, and recent studies suggest that their activation may alleviate motor deficits. This study investigates the effects of chemogenetic activation of PV interneurons on cisplatin-induced muscle atrophy and motor dysfunction in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type C57BL/6 mice and transgenic hM3Dq mice were used in this study. Cisplatin (3 mg/kg) was administered intraperitoneally for 7 days to induce muscle atrophy. Mice were then treated with clozapine-n-oxide (CNO) to activate PV interneurons. Muscle strength and endurance were assessed using grip strength measurements, the inverted grid test and the wire hang test. Neuromuscular junction (NMJ) integrity was examined via histological analysis. Exercise intervention was also included, using a treadmill with a 15° incline for 60 min at varying speeds during seven consecutively days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cisplatin treatment significantly reduced body weight (<i>p</i> < 0.001), grip strength (forelimb strength: <i>p</i> < 0.001, four-limb strength: <i>p</i> < 0.001), endurance (inverted grid test: <i>p</i> = 0.047, wire hang test: <i>p</i> = 0.014) and NMJ integrity (partially innervated NMJs: <i>p</i> = 0.0383). PV interneuron activation with CNO improved spontaneous motor activity in cisplatin-treated mice, as evidenced by a significant increase in total travel distance (<i>p</i> = 0.049) in the open-field test. Histological analysis showed a reduced ratio of partially innervated NMJs in the PV-cre group compared to the control virus group (<i>p</i> = 0.0441). Muscle strength also improved significantly, with forelimb grip strength increased (<i>p</i> < 0.001) and four-limb grip strength increased (<i>p</i> = 0.018). Muscle wet-weight ratios were significantly higher in the PV-cre group (quadriceps: <i>p</i> = 0.030). Exercise intervention significantly improved grip strength (forelimb: <i>p</i> < 0.001, four-limb: <i>p</i> = 0.002), muscle endurance (four-limb hang test: <i>p</i> = 0.048) and muscle weight (quadriceps: <i>p</i> = 0.015, gastrocnemius: <i>p</i> = 0.022), with an increase in muscle fibre cross-sectional area (<i>p</i> = 0.0018).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13782","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793399","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 Controlled ‘REAL-FITNESS’ Trial to Evaluate Physical Activity in Patients With Newly Diagnosed Multiple Myeloma","authors":"Esther Dreyling, Jan Räder, Mandy-Deborah Möller, Gabriele Ihorst, Sina Wenger, Antonia Pahl, Jann Arends, Georg Herget, Peter Deibert, Ralph Wäsch, Monika Engelhardt","doi":"10.1002/jcsm.13793","DOIUrl":"https://doi.org/10.1002/jcsm.13793","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multiple myeloma (MM) is the second most common haematological malignancy. The predominantly older patients often suffer from comorbidities that impair their quality of life (QoL). Physical activity (PA) can be beneficial for cancer patients, but less evidence exists in MM. This randomized controlled trial (RCT) compared an exercise group with World Health Organization (WHO)–compliant PA (150 min aerobic exercise and 2 resistance training-sessions/week) vs. activity as usual (control group).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-four newly diagnosed consecutive MM patients were randomized 1:1 to exercise vs. control groups. Guided training (2×/week) was performed for 3 months during bortezomib–cyclophosphamide–dexamethasone (VCd) induction. PA was monitored using smartwatches and diaries. Demographics, osteolytic lesions, infections, fatigue, depression, and biomarkers (albumin, creatine kinase, C-reactive protein, high-density lipoprotein, low-density lipoprotein and pro-brain natriuretic peptide) were compared in exercise vs. control cohorts. VCd-tolerance, response, ‘timed-up-and-go-test’ (TUGT), Revised Myeloma Comorbidity Index (R-MCI), QoL (SF-12 questionnaire), event-free survival and trainer assignment during the training period were assessed (13 tests at baseline, during VCd and end of treatment [EOT]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The exercise group was more than twice as active as the control group, with an average aerobic activity of 162 versus 68 min/week, respectively. Trainer-guided muscle-strengthening exercises were performed 2×/week in the exercise group, in line with WHO recommendations. These data were monitored via smartwatches and training diaries. PA proved to be safe: No exercise-related SAEs or accidents occurred. The study adherence was 94% (32/34). In the exercise versus control group, AEs to VCd induction (6% vs. 25%), therapy intolerance (6% vs. 25%) and hospitalization (31% vs. 50%, respectively) occurred less frequently. VCd-dose adjustments in the exercise vs. control group were significantly less needed (6.3% vs. 37.5%, respectively). At EOT, patients in the exercise group showed less fatigue (6% vs. 75%), less depression (6% vs. 44%), better TUGT (6 vs. 11 s, respectively), improved R-MCI and QoL compared to the control group. Grip strength (right hand: 73–82 lb; left hand: 68–72 lb) significantly improved from baseline to EOT in the exercise group. Biomarkers did not significantly differ in both groups, but response to VCd-induction and event-free survival were improved in the exercise group, however, without reaching statistical significance.","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793540","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":"Osteosarcopenia in Chronic Kidney Disease: An Overlooked Syndrome?","authors":"Lara Caldiroli, Paolo Molinari, Claudia D'Alessandro, Adamasco Cupisti, Carlo Alfieri, Giuseppe Castellano, Simone Vettoretti","doi":"10.1002/jcsm.13787","DOIUrl":"https://doi.org/10.1002/jcsm.13787","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Healthy ageing relies on maintaining physiological systems, particularly the musculoskeletal system (MKS). After 50, declines in bone density, muscle mass and strength increase the risk of osteoporosis and sarcopenia, leading to frailty, fractures and higher healthcare costs. Osteosarcopenia, combining osteoporosis and sarcopenia, is rising because of the ageing population. Chronic kidney disease (CKD) exacerbates this condition through disruptions in mineral metabolism, hormonal imbalances and inflammation, further compromising musculoskeletal health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review examines the pathophysiology of osteosarcopenia associated with CKD, focusing on the role of mineral and hormonal disturbances, chronic inflammation and endocrine dysfunction. It aims to increase clinical awareness and highlight the need for early diagnosis and intervention to mitigate the burden of osteosarcopenia on the quality of life and healthcare systems in ageing CKD populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative review of the current literature was conducted, summarising evidence on the mechanisms underlying osteosarcopenia in CKD, including mineral metabolism alterations, inflammatory processes and hormonal imbalances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Osteosarcopenia is a recognised consequence of CKD, contributing to increased morbidity and mortality. The pathophysiology of osteosarcopenia in CKD is multifactorial, involving disruptions in mineral metabolism, inflammation, endocrine dysfunction and physical inactivity. CKD–mineral and bone disorder (CKD-MBD) leads to alterations in calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and vitamin D metabolism, resulting in impaired bone mineralisation and increased fracture risk. Simultaneously, CKD accelerates muscle wasting through systemic inflammation, anabolic resistance and metabolic derangements, increasing the risk of sarcopenia. Sarcopenic obesity, inflammaging and hormonal dysregulation further exacerbate bone muscle deterioration. Emerging evidence suggests that osteosarcopenia in CKD is a consequence of interconnected pathophysiological pathways rather than isolated conditions. Diagnosis remains challenging because of overlapping clinical features, necessitating integrated assessment tools. Targeted therapeutic strategies, including mineral metabolism correction, resistance exercise and anabolic interventions, are essential to mitigate osteosarcopenia's progression and ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786788","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":"Multitrajectories of Frailty and Depression With Cognitive Function: Findings From the Health and Retirement Longitudinal Study","authors":"Chengxiang Hu,&nbsp;Xiaoyue Sun,&nbsp;Zhirong Li,&nbsp;Yue He,&nbsp;Beibei Han,&nbsp;Zibo Wu,&nbsp;Siyu Liu,&nbsp;Lina Jin","doi":"10.1002/jcsm.13795","DOIUrl":"https://doi.org/10.1002/jcsm.13795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Little is known about the joint associations between trajectories of frailty and depression with cognitive function. This study aims to explore the multitrajectories of frailty and depression and their joint impact on cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 8600 participants from the Health and Retirement Study (HRS) (1996–2018) were analysed using a group-based trajectory model for 10-year multitrajectories. Participants were classified into five groups based on their trajectories. Multivariable linear mixed models and Cox proportional hazards models were utilized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with Group 1 (stable robust and nondepressed), Groups 2 (‘worsening prefrailty without depression,’ <i>β</i> = −0.022 SD/year), 3 (‘stable prefrailty with escalating depressive symptoms,’ <i>β</i> = −0.016 SD/year), 4 (‘increasing frailty alongside worsening depressive symptoms,’ <i>β</i> = −0.034 SD/year) and 5 (‘high and escalating frailty with persistent depression,’ <i>β</i> = −0.055 SD/year) exhibited accelerated cognitive decline. Dementia risk was significantly higher in G2 (HR = 1.26, 95% CI: 1.08–1.48), G3 (HR = 1.54, 95% CI: 1.31–1.80), G4 (HR = 1.81, 95% CI: 1.54–2.14) and G5 (HR = 1.86, 95% CI: 1.48–2.33) compared with G1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Worsening frailty and depression accelerate cognitive decline and risk of dementia, underscoring the need to address both conditions to mitigate cognition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787053","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":"Association of Dietary Choline Intake With Incidence of Frailty: A Nationwide Prospective Cohort Study From China","authors":"Lian-hong Chen,&nbsp;Jian-feng Zhong,&nbsp;Ying-ying Niu,&nbsp;Cheng-ping Li,&nbsp;Jing Li,&nbsp;Zhi-quan Diao,&nbsp;Hao-yu Yan,&nbsp;Miao Xu,&nbsp;Wen-qi Huang,&nbsp;Zhi-tong Xu,&nbsp;Chang Su,&nbsp;Dan Liu","doi":"10.1002/jcsm.13796","DOIUrl":"https://doi.org/10.1002/jcsm.13796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emerging evidence suggests that dietary choline is a modifiable nutritional factor linked to various health outcomes. However, most existing studies have focused on isolated health conditions, lacking a comprehensive assessment of overall health status. This study aimed to investigate the association between total dietary choline intake and frailty incidence among Chinese adults, considering its derivatives, soluble forms (water-soluble and lipid-soluble) and food sources (animal-derived and plant-derived).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants without frailty at baseline were enrolled from the China Health and Nutrition Survey (CHNS), with follow-up from 2004 to 2016. Dietary intake was assessed using three consecutive 24-h dietary recalls to estimate total dietary choline intake, its derivatives, soluble forms and food sources. Frailty status was evaluated using a frailty index (FI), with frailty defined as an FI &gt; 0.21. Cox proportional hazards regression and restricted cubic splines were used to analyse the associations between dietary choline intake and frailty incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 10 310 participants (mean age: 46.4 years [SD: 14.5]; 52.6% female) were eligible. During a median follow-up of 6.1 years, 1150 incident frailty cases were recorded. Cox models with penalized splines showed an L-shaped association between total dietary choline intake and frailty incidence. Compared with participants in the lowest quartile of total choline intake, those in the 2nd to 4th quartiles had lower odds of frailty, with hazard ratios (HRs) of 0.84 (95% CI: 0.71, 0.98), 0.80 (95% CI: 0.67, 0.95) and 0.75 (95% CI: 0.61, 0.93), respectively. Intake of lipid-soluble choline in the 2nd to 4th quartiles was associated with an 18% (HR: 0.82; 95% CI: 0.69, 0.98) to 23% (HR: 0.77; 95% CI: 0.63, 0.95) reduction in the odds of frailty. Participants in the 3rd to 4th quartiles of phosphatidylcholine intake exhibited 19% (HR: 0.81; 95% CI: 0.68, 0.96) to 23% (HR: 0.77; 95% CI: 0.63, 0.94) lower odds of frailty. Choline intake from plant-derived food sources was significantly associated with reduced odds of frailty (HR: 0.83; 95% CI: 0.69, 0.99).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Moderate to high dietary choline intake (171.00–464.99 mg/day), particularly phosphatidylcholine (145.20–304.93 mg/day), may be associated with reduced odds of frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787054","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":"Nestin Regulates Autophagy-Dependent Ferroptosis Mediated Skeletal Muscle Atrophy by Ubiquitinating MAP 1LC3B","authors":"Shunshun Han,&nbsp;Xiyu Zhao,&nbsp;Chunlin Yu,&nbsp;Can Cui,&nbsp;Yao Zhang,&nbsp;Qing Zhu,&nbsp;Mohan Qiu,&nbsp;Chaowu Yang,&nbsp;Huadong Yin","doi":"10.1002/jcsm.13779","DOIUrl":"https://doi.org/10.1002/jcsm.13779","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Programmed cell death plays a critical role in skeletal muscle atrophy. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various diseases, but its role in skeletal muscle atrophy remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ferroptosis in skeletal muscle atrophy was investigated using two models: dexamethasone (Dex)-induced atrophy (<i>n</i> = 6 independent cell cultures per group) and simulated microgravity (<i>n</i> = 6 mice per group). Conditional Nestin knockout (KO) mice were generated using CRISPR/Cas9 (<i>n</i> = 6–8 mice per group), with wild-type (WT) controls (<i>n</i> = 6–8). Phenotypic analyses included histopathology (HE staining), functional assessments (muscle strength, weight analysis, treadmill), and dystrophy evaluation (dystrophin staining). Molecular analyses involved flow cytometry, ELISA, transmission electron microscopy, PI staining, and IP/MS to delineate Nestin-regulated ferroptosis pathways in skeletal muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ferroptosis was significantly activated in both atrophy models, with a 2.5-fold increase in lipid peroxidation (<i>p</i> &lt; 0.01), a 2-fold accumulation of Fe²⁺ (<i>p</i> &lt; 0.01) and a 50% reduction in Nestin expression (<i>p</i> &lt; 0.001). Nestin KO mice exhibited exacerbated muscle atrophy, showing a 40% decrease in muscle weight (<i>p</i> &lt; 0.01) and a 30% reduction in muscle strength (<i>p</i> &lt; 0.05) compared to WT mice. Nestin overexpression mitigated Dex-induced ferroptosis, reducing lipid peroxidation by 40%, decreasing Fe²⁺ accumulation by 50% (<i>p</i> &lt; 0.01), and improving muscle function by 30% (<i>p</i> &lt; 0.05). Mechanistically, Nestin interacted with MAP 1LC3B (LC3B) to catalyse LC3B polyubiquitination at lysine-51, reducing LC3B availability for autophagy and inhibiting autophagy flux by 60% (<i>p</i> &lt; 0.01), leading to a 50% reduction in ferroptosis (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study identifies Nestin as a critical regulator of ferroptosis-autophagy crosstalk in skeletal muscle atrophy. Targeting Nestin-LC3B ubiquitination may offer novel therapeutic strategies for preventing muscle wasting in diseases such as cachexia and sarcopenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770098","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":"Calcium Handling Machinery and Sarcomere Assembly are Impaired Through Multipronged Mechanisms in Cancer Cytokine-Induced Cachexia","authors":"Luis Vincens Gand,&nbsp;Chiara Lanzuolo,&nbsp;Mugeng Li,&nbsp;Valentina Rosti,&nbsp;Natalie Weber,&nbsp;Dongchao Lu,&nbsp;Christian Bär,&nbsp;Thomas Thum,&nbsp;Andreas Pich,&nbsp;Theresia Kraft,&nbsp;Mamta Amrute-Nayak,&nbsp;Arnab Nayak","doi":"10.1002/jcsm.13776","DOIUrl":"https://doi.org/10.1002/jcsm.13776","url":null,"abstract":"&lt;p&gt;The precisely arranged sarcomeres are the fundamental units of striated muscle cells that produce force from ATP-dependent cross-bridge cycling between actin (thin filaments) and myosin (thick filaments) to bear load and drive movement. During excitation–contraction coupling (ECC) process, calcium (Ca&lt;sup&gt;2+&lt;/sup&gt;) is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR1), activating thin filament and enabling acto-myosin cross-bridge cycling, and hence myocyte contraction [&lt;span&gt;1, 2&lt;/span&gt;]. The dihydropyridine receptor (DHPR) α1s subunit physically interacts with RyR1, inducing an opening of the channel as the result of an action potential [&lt;span&gt;1&lt;/span&gt;]. Muscle relaxation follows the transfer of Ca&lt;sup&gt;2+&lt;/sup&gt; ions to the SR through the calcium ATPase pump SERCA1. Thus, a precise sarcomeric assembly, a proper Ca&lt;sup&gt;2+&lt;/sup&gt; transient, and correct interplay between these two systems is critical for primary muscle cell functions, i.e., contraction and force generation. Molecular insights in various aspects of these processes remain poorly determined. A detailed understanding of it is critical to apprehend not only muscle physiology but muscle wasting conditions as well.&lt;/p&gt;&lt;p&gt;Cancer triggers cachexia, which is a severe muscle wasting disorder associated with up to 80% of cancer patients [&lt;span&gt;3&lt;/span&gt;]. Cancer cytokine-induced cachexia (CIC) is defined by ongoing involuntary loss of muscle and/or fat mass and is not reversible by common treatments [&lt;span&gt;4&lt;/span&gt;], with an estimated high mortality rate ranges from 20% to 50% in cancer patients depending on cancer types [&lt;span&gt;5&lt;/span&gt;]. The effective dose of cancer therapeutics, particularly chemotherapy, is calculated based on body surface area [&lt;span&gt;6, 7&lt;/span&gt;]. Thus, CIC additionally aggravates the patient's responsiveness to therapies [&lt;span&gt;8&lt;/span&gt;]. Tumour-released pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α), interferon gamma (INF-γ), interleukin 6 (IL-6), induce degradation of myofibril proteins, especially myosin heavy chain (MyHC), through NF-κB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells)-MuRF1 (muscle RING-finger protein-1) ubiquitin-proteasome pathway [&lt;span&gt;9&lt;/span&gt;]. Furthermore, NF-κB downregulates the master transcription factor MyoD and thereby suppresses skeletal muscle differentiation of myogenic progenitor cells [&lt;span&gt;10, 11&lt;/span&gt;]. Besides Murf1, other E3 ligases including Atrogin1 and UBR2 are also upregulated and modify thick filament proteins for degradation [&lt;span&gt;12, 13&lt;/span&gt;]. Pro-inflammatory cytokines also contribute to insulin resistance and suppression of the insulin-like growth factor I (IGF1)-Akt pathway, further deteriorating the catabolic condition [&lt;span&gt;14&lt;/span&gt;]. Moreover, upregulation of the metal-ion transporter ZRT- and IRT-like protein 14 (ZIP14) has been shown in cachectic skeletal muscles of mice and in human patients with metastatic cancer in response to ca","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13776","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770123","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":"Prediction Models for Risk of Cardiorespiratory Morbidity/Mortality and Fracture Among Young Adults With Cerebral Palsy","authors":"Daniel G. Whitney,&nbsp;Edward A. Hurvitz","doi":"10.1002/jcsm.13640","DOIUrl":"https://doi.org/10.1002/jcsm.13640","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;There is a dearth of screening tools for cardiorespiratory disease and fracture risk, such as risk prediction models, for adults with cerebral palsy (CP). There is heterogeneity of pathophysiology related to the severity of CP and aging, such that a suite of risk prediction models may be needed. Differentiating by sarcopenia versus frailty syndromes may be a useful, physiologic-based framework to develop a suite of cardiorespiratory disease and fracture risk prediction models for adults with CP. The study objective was to determine if risk prediction models including widely available variables that are CP non-specific and that may capture the physiologic components of frailty provide clinically useful prediction of salient health issues for young adults with CP.&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 retrospective cohort study used medical records from 01/01/2012 to 10/2/2022 from 18–40-year-olds with CP at a single Medical Centre. Logistic regression models were developed for three separate outcomes: 3-year risk of respiratory morbidity/mortality, cardiovascular morbidity/mortality and fracture. The following predictors were included: age, sex, intellectual disabilities, epilepsy and four serum biomarkers (creatinine, glucose, calcium, carbon dioxide) from the clinical Basic/Comprehensive Metabolic Panel assay. Model performance measures were evaluated, including discrimination (c-statistic) and calibration. Internal validation was assessed, and optimism-corrected c-statistics were computed using the bootstrap resampling method to assess model overfitting.&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;There were 805 young adults with CP with an average (SD) age of 26.5 (6.6) years and 47.8% were female. Over the 3-year follow-up, 24.6% had incident respiratory morbidity/mortality, 8.9% had incident cardiovascular morbidity/mortality and 7.0% had an incident fracture. The c-statistic (95% CI) was 0.74 (0.70–0.78) for respiratory morbidity/mortality, 0.63 (0.57–0.70) for cardiovascular morbidity/mortality and 0.65 (0.58–0.73) for fracture. The optimism-corrected c-statistic was similar for respiratory morbidity/mortality (0.73) but lower for cardiovascular morbidity/mortality (0.58) and fracture (0.59), suggesting evidence of model overfitting. All models showed good calibration based on the slope of the predicted risk versus observed risk around 1.0 and the Hosmer–Lemeshow goodness-of-fit test, &lt;i&gt;P&lt;/i&gt; = 0.305–0.903. However, the range of predicted risks was limited to ~20% for cardiovascular morbidity/mortality and ~55% for fracture, suggesting that these models have limited value for those with","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770411","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":"Long-Term Effects of High-Intensity Aerobic Training on Metabolic Syndrome: An 8-Year Follow-Up Randomized Clinical Trial","authors":"Felix Morales-Palomo,&nbsp;Alfonso Moreno-Cabañas,&nbsp;Laura Alvarez-Jimenez,&nbsp;Diego Mora-Gonzalez,&nbsp;Ricardo Mora-Rodriguez","doi":"10.1002/jcsm.13780","DOIUrl":"https://doi.org/10.1002/jcsm.13780","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;Metabolic syndrome (MetS) is a set of five cardiometabolic risk factors that typically worsen with age. One exercise-training programme is effective at improving those factors in middle-aged individuals with MetS. To our knowledge, exercise-training efficacy as MetS individuals age has not been explored. This study determined the effectiveness of a periodized exercise training programme for individuals with MetS after a follow-up period of 8 years.&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;Forty-seven individuals with MetS were block-randomized into an EXERCISE (&lt;i&gt;n&lt;/i&gt; = 22, 52 ± 8 years old, 23% women) or a CONTROL group (&lt;i&gt;n&lt;/i&gt; = 25, 53 ± 8 years old, 32% women). Both groups received standard health care, including medical counselling and lifestyle advice at least every 6 months, while participants in EXERCISE also underwent a supervised exercise programme. The intervention lasted 8 years and consisted of 4 months per year (November to March) of high-intensity interval training thrice weekly. At baseline, and after 4 and 8 years of treatment, we assessed body composition, MetS components (i.e., MetS &lt;i&gt;Z&lt;/i&gt; score), medication use, cardiorespiratory fitness (CRF; assessed by VO&lt;sub&gt;2MAX&lt;/sub&gt;) and maximal leg cycling power output (W&lt;sub&gt;MAX&lt;/sub&gt;).&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;Paradoxically, MetS &lt;i&gt;Z&lt;/i&gt; score and body weight were reduced after 8 years (subjects aged from 52 to 60 years old) in both groups (time effect &lt;i&gt;p&lt;/i&gt; &lt; 0.001 and &lt;i&gt;p&lt;/i&gt; = 0.008; time × group interaction &lt;i&gt;p&lt;/i&gt; = 0.253 and &lt;i&gt;p&lt;/i&gt; = 0.130). However, in those 8 years, the medicine use score increased threefold in CONTROL (137% increase; from 1.7 to 3.9; &lt;i&gt;p&lt;/i&gt; &lt; 0.001) while it did not change in EXERCISE (33%; from 2.0 to 2.7; &lt;i&gt;p&lt;/i&gt; = 0.066). In 8 years, CRF and W&lt;sub&gt;MAX&lt;/sub&gt; increased in EXERCISE by 14% (3.4 ± 5.6 mL·kg&lt;sup&gt;−1&lt;/sup&gt;·min&lt;sup&gt;−1&lt;/sup&gt;) and 4% (7 ± 37 W) while decreasing in CONTROL by −7% (−1.6 ± 3.4 mL·kg&lt;sup&gt;−1&lt;/sup&gt;·min&lt;sup&gt;−1&lt;/sup&gt;) and −14% (−24 ± 27 W) being different between groups after 4 and 8 years (both time × group interaction &lt;i&gt;p&lt;/i&gt; = 0.002). Pearson correlations showed that MetS &lt;i&gt;Z&lt;/i&gt; score improvements were significantly associated with increases in medication use score in the CONTROL group (&lt;i&gt;r&lt;/i&gt; = 0.491; &lt;i&gt;p&lt;/i&gt; = 0.013) and with W&lt;sub&gt;MAX&lt;/sub&gt; enhancement in the EXERCISE group (&lt;i&gt;r&lt;/i&gt; = 0.613; &lt;i&gt;p&lt;/i&gt; = 0.002).&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 data suggest that annual exercise training has similar clinical efficacy to tripl","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749855","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}