Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Nicotinamide Phosphoribosyltransferase Acetylation Mediating Muscle Dysfunction Contributes to Sleep Apnoea in Obesity","authors":"Liu Zhang,&nbsp;Ya Ru Yan,&nbsp;Shi Qi Li,&nbsp;Ying Ni Lin,&nbsp;Yi Wang,&nbsp;Yu Qing Wang,&nbsp;Ning Li,&nbsp;Fang Ying Lu,&nbsp;Xian Wen Sun,&nbsp;Li Yue Zhang,&nbsp;Jian Ping Zhou,&nbsp;Yong Jie Ding,&nbsp;Qing Yun Li","doi":"10.1002/jcsm.13693","DOIUrl":"10.1002/jcsm.13693","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obstructive sleep apnoea (OSA) occurs frequently among individuals with obesity, which is attributed to upper airway muscle dysfunction. Muscle function is regulated by the dynamic balance of the nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH), which is controlled by the enzyme nicotinamide phosphoribosyltransferase (NAMPT). Elevated NAMPT levels have been found in individuals with obesity. However, the role of NAMPT in obesity-induced muscle impairment has not been fully clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 110 participants (70 moderate-to-severe OSA vs. 40 mild or no OSA) underwent electrical impedance mammography and polysomnography. C57BL/6J mice with high-fat diet-induced obesity (DIO) and control group were utilized for their characterizations, which included forced running wheel tests, glucose tolerance tests, haematoxylin and eosin staining, immunostaining, magnetic resonance imaging, whole-body plethysmography, electromyographic techniques, western blot, NAMPT enzymatic activity assays and NAD+/NADH ratio measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with moderate–severe OSA have a significant decrease in lean mass percentage of upper airway muscles compared with those in controls (<i>p</i> &lt; 0.01). In vivo, a high-fat diet reduced the levels of NAD-dependent deacetylase sirtuin-1 (SIRT1) (<i>p</i> &lt; 0.01), which plays a crucial role in the deacetylation of NAMPT. The reduction in SIRT1-mediated NAMPT deacetylation (<i>p</i> &lt; 0.001) resulted in decreased NAMPT activity (<i>p</i> &lt; 0.01), leading to a decrease in NAD+/NADH ratio (<i>p</i> &lt; 0.05) and decreased the myosin heavy chain isoform (MyHC) I level (<i>p</i> &lt; 0.05), thereby affecting the effectiveness of upper airway muscle and ultimately leading to upper airway collapse (101.0 vs. 81.7 pixels, <i>p</i> = 0.02). The introduction of estradiol mitigated high-fat diet-induced muscle dysfunction by enhancing expression of SIRT1 and inhibiting the acetylation of NAMPT, reducing upper airway collapse (81.7 vs. 96.7 pixels, <i>p</i> = 0.06).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the crucial role of SIRT1-mediated NAMPT deacetylation on obesity-induced muscle dysfunction, suggesting targeting NAMPT has the potential to reverse the obesity induced muscle dysfunction and provide effective treatment options for OSA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084078","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":"Prevalence and Prognostic Significance of Sarcopenia in Gynecologic Oncology: A Systematic Review and Meta-Analysis","authors":"Chen Jiang,&nbsp;Qin Chen,&nbsp;Danping Yu,&nbsp;Qianqian Zhou,&nbsp;Cong Tang,&nbsp;Chenping Qiao","doi":"10.1002/jcsm.13699","DOIUrl":"10.1002/jcsm.13699","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia in gynaecologic oncology patients has garnered increasing attention, but its prevalence has not been comprehensively summarized. This study aims to integrate the prevalence of sarcopenia in this population through systematic evaluation and meta-analysis, providing a reference for future clinical research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A computerized search of PubMed, Embase, The Cochrane Library, Web of Science and other databases was conducted to collect relevant literature on the prevalence of sarcopenia in gynaecologic oncology patients and its impact on prognosis, with a timeframe from the inception of the databases to July 2024. Two researchers independently screened the literature, extracted information and assessed the risk of bias. After evaluating the risk of bias, a meta-analysis was performed using RevMan5.4 software. This systematic review was conducted using a previously published study protocol (PROSPERO: CRD42024565094).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 24 studies encompassing 4136 patients were included. The meta-analysis revealed that the prevalence of sarcopenia in gynaecologic oncology patients was 38.8% (<i>I</i>² = 96%, 95% CI [0.49–0.79], <i>p</i> &lt; 0.001). Subgroup analysis indicated that the prevalence of sarcopenia was higher among patients with endometrial cancer or ovarian cancer, those over 60 years of age, individuals with a body mass index (BMI) greater than 25 kg/m², those diagnosed using the psoas muscle index (PMI) and patients assessed at the L4 vertebra. Overall survival (OS) was significantly lower in patients with gynaecologic tumours combined with sarcopenia compared to those with gynaecologic tumours alone. However, no significant differences were observed in progression-free survival (PFS), mortality or length of hospital stay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sarcopenia has a high prevalence in gynaecologic oncology patients. Healthcare professionals should prioritize early screening and preventive measures for high-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076840","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":"Fat-Free Mass: Friend or Foe to Metabolic Health?","authors":"Christopher J. Oliver,&nbsp;Mike Climstein,&nbsp;Nedeljka Rosic,&nbsp;Anja Bosy-Westphal,&nbsp;Grant Tinsley,&nbsp;Stephen Myers","doi":"10.1002/jcsm.13714","DOIUrl":"10.1002/jcsm.13714","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;Fat mass (FM) and fat-free mass (FFM) are body composition estimates commonly reported in research studies and clinical settings. Recently, fat-free mass indexed to height (fat-free mass index; FFMI) has been shown to be positively associated with impaired insulin sensitivity or insulin resistance. Consequently, hypertrophic resistance training which can increase FFM was also questioned. This paper sets out to evaluate these propositions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this narrative review, we discuss possible reasons that link FFMI to adverse metabolic health outcomes including the limitations of the body composition model that utilizes FFM. The safety of resistance training is also briefly discussed.&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;Approximately 50% of FFM is comprised of skeletal muscle (SM), with the other 50% being viscera, skin, and bone; FFM and SM cannot be conflated. FFM and fat mass (FM) can both rise with increasing body weight and adiposity, indicating a positive correlation between the two compartments. Risk assessment models not adequately adjusting for this correlation may cause erroneous conclusions, however which way FM and FFM are indexed. Adipose tissue accumulation with weight gain, measured by dual-energy X-ray absorptiometry or bioelectrical impedance, can inflate FFM estimates owing to increased connective tissue. Increased adiposity can also result in fat deposition within skeletal muscle disrupting metabolic health. Importantly, non-skeletal muscle components of the FFM, i.e., the liver and pancreas, both critical in metabolic health, can also be negatively affected by the same lifestyle factors that impact SM. The most frequently used body composition techniques used to estimate FM and FFM cannot detect muscle, liver or pancreas fat infiltration. Prospective evidence demonstrates that resistance training is a safe and effective exercise modality across all ages, especially in older adults experiencing age- or disease-related declines in muscle health.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The association between FFM and insulin resistance is largely an artefact driven by inadequate assessment of skeletal muscle. If FM and FFM are used, at the minimum, they need to be evaluated in context with one another. Body composition methods, such as magnetic resonance imaging, which measures skeletal muscle rather than fat-free mass, and adipose tissue as well as muscle ectopic fat, are preferred methods. Resistance training is important in achieving","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076829","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":"The Effect of Exercise on Spexin and Follistatin in Elderly Individuals","authors":"Elif Yıldırım Ayaz,&nbsp;Berna Dincer,&nbsp;Gülser Cinbaz,&nbsp;Esra Karacan,&nbsp;Reyhan Kaygusuz Benli,&nbsp;Emel Mete,&nbsp;Hilal Bilgiç,&nbsp;Banu Mesci","doi":"10.1002/jcsm.13692","DOIUrl":"10.1002/jcsm.13692","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;In adipose tissue–muscle crosstalk mechanisms, the interaction of adipokines and myokines is known to be critical for maintaining the body's metabolic balance in age-related metabolic disorders. The aim of the study investigate the effects of 12 weeks of aerobic and resistance exercise training on spexin and follistatin and their relationship with each other.&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 study was a multicentre, randomized controlled study conducted at two assisted living facilities with participants aged ≥ 65. Among the 66 subjects, 33 were allocated to the exercise group (E) and 33 to the control group (C). The exercise group was administered 50 min of exercise by expert physiotherapists 1 day a week for 12 weeks. Participants in the intervention groups performed exercise assignments two extra days a week, tailored to their specific circumstances and supervised by the institution's physiotherapists. Spexin, follistatin and measurements of metabolic syndrome parameters were performed at the beginning and after 12 weeks.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The mean age of the 62 participants who completed the study (E &lt;i&gt;n&lt;/i&gt; = 31, C &lt;i&gt;n&lt;/i&gt; = 31) was 73.25 ± 6.44 years, and 62.9% were female. While spexin (E = 1090.94 ± 533.66, C = 1142.91 ± 550.68 pg/mL, &lt;i&gt;p&lt;/i&gt; &gt; 0.05) and follistatin (E = 50.52 ± 24.35, C = 50.00 ± 23.52 ng/mL, &lt;i&gt;p&lt;/i&gt; &gt; 0.05) values were similar in the two groups at baseline, the values of spexin (E = 1311.32 ± 513.66, C = 1033.27 ± 486.48, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.387) and follistatin (E = 64.79 ± 32.35, C = 48.16 ± 26.27, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.267) in the exercise group were higher than in the control group at week 12. At the 12th week, neck circumference (38.32 ± 3.41, 37.16 ± 3.15, &lt;i&gt;p&lt;/i&gt; = 0.002), waist circumference (102.64 ± 13.38, 98.54 ± 14.47, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), hip circumference (105.70 ± 15.43, 102.93 ± 13.48, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), body fat mass (22.69 ± 7.39, 20.45 ± 6.22, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and systolic and diastolic blood pressure (137.19 ± 13.80, 124.9 ± 15.18, &lt;i&gt;p&lt;/i&gt; = 0.0001, 77.38 ± 12.10, 72.61 ± 9.26, &lt;i&gt;p&lt;/i&gt; = 0.043) decreased, and body muscle mass (46.32 ± 8.43, 49.03 ± 8.58, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) increased in the exercise group compared to baseline. A correlation was observed between the change in follistatin level and the change in spexin level (&lt;i&gt;r&lt;/i&gt; = 0.438, &lt;i&gt;p&lt;/i&gt; = 0.001). A negative correlation was found between the amount of decrease in body fat mass and the decrease in spexin level (&lt;i&gt;r&lt;/i&gt; = −0.380, &lt;i&gt;p&lt;/i&gt; = 0.005). A positive correlation was foun","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076839","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":"Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice","authors":"Jeong Hwan Park,&nbsp;Jongsoo Mok,&nbsp;Seoah Park,&nbsp;Dooho Kim,&nbsp;Min-Su Kang,&nbsp;Tae Sub Park,&nbsp;Joonghoon Park","doi":"10.1002/jcsm.13704","DOIUrl":"10.1002/jcsm.13704","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;Muscle diseases are serious challenges to human health. Prokineticin receptor 1 (PROKR1) has emerged as a potential target to improve muscle function through increasing oxidative muscle fibres, but there are no clinically applicable synthetic PROKR1 agonists.&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;Drugs with biological properties of prokineticin 2 (PK2) were discovered through connectivity map (CMap) analysis. Their effects on PROKR1 were evaluated using molecular docking, PROKR1 signalling and competitive binding assays. Pregnant dams were fed diets containing varying celecoxib concentrations (0, 500, 1000 and 1500 ppm) from gestation day 5 through weaning. Offspring were given high-fat diets (HFD) from weaning until 20 weeks old, and body composition, insulin resistance, energy expenditure, exercise performance and histological analysis of muscle tissues were evaluated.&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;Celecoxib, with a connectivity score of 64.19 to PK2 and a docking score of −9.0 to PROKR1, selectively activated Gs signalling at 4 μM of EC&lt;sub&gt;50&lt;/sub&gt; and increased NR4A2 protein levels by 1.6-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) in PROKR1-overexpressing cells. It competitively inhibited PK2 binding to PROKR1 and reduced cAMP accumulation. In murine and human myotubes, celecoxib increased Prokr1 protein levels by 1.8-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), pCreb by 1.5-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and Nr4a2 by 1.3-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). It also elevated Myh7 index by 2.2-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), mitochondrial content by 1.6-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and fatty acid oxidation (FAO) activity by 4.1-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Offspring exposed to celecoxib during pre- and postnatal muscle development exhibited activated Prokr1 signalling, enhanced oxidative muscle fibre formation and improved muscle phenotype despite HFD. At weaning, both male and female offspring showed dose-dependent increases in lean mass (&gt; 9.35%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and grip strength (&lt; 18.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). At 12 weeks old, mice displayed a dose-dependent decrease in weight loss (&gt; 13.3%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), increased lean mass (&gt; 16.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), improved insulin resistance (&gt; 70.4%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), energy expenditure (&gt; 173%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and grip strength (&gt; 23.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Celecoxib also increased Myh7-positive muscle fibre composition (&gt; 10.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and mitochondrial mass (&gt; 32.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) in the gastrocnemius and soleus muscles, accompanied by significant Prokr1 signalling activation. These effects persisted in both male and fem","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056612","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":"C-Terminal Agrin Fragment as a Biomarker for Sarcopenia: A Systematic Review and Meta-Analysis","authors":"Rida Fatima,&nbsp;Yonghoon Kim,&nbsp;Suhyeon Baek,&nbsp;Reema Priyanka Suram,&nbsp;Sun-Joung Leigh An,&nbsp;Yonggeun Hong","doi":"10.1002/jcsm.13707","DOIUrl":"10.1002/jcsm.13707","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Sarcopenia is a gradual decline in skeletal muscle mass and strength, which eventually leads to reduced physical performance. 50% of people aged 60–80 years suffer from sarcopenia. Considering the devastating outcomes and the importance of promoting healthy ageing, the diagnosis and prevention of sarcopenia is of utmost importance. Recently, C-terminal agrin fragment (CAF) has been identified as an indicator for early diagnosis of sarcopenia. So far, systematic reviews demonstrating CAF as a biomarker for sarcopenia have been conducted, but a meta-analysis is still needed. This study contains systematic review as well as detailed meta-analysis to better understand the association of CAF and sarcopenia.&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;Articles were primarily obtained from four different databases. Studies demonstrating the association between CAF and sarcopenia were selected. Data extraction and analysis were performed using STATASE 16 software. The risk of bias and quality assessment of each study was carried out using Joanna Briggs Institute (JBI) Critical Appraisal Tool. Meta-regression, subgroup and sensitivity analysis were conducted to identify the source of heterogeneity.&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;Seventeen studies were included in the qualitative analysis, out of which 10 were included in the quantitative analysis. The meta-analysis showed that CAF levels were significantly higher in sarcopenia patients, with an effect size of 1.93 (ROM = 1.93, 95% CI [1.49 to 2.36]; &lt;i&gt;p&lt;/i&gt; = 0.00) and 1.38 (ROM = 1.38, 95% CI [0.94 to 1.83], &lt;i&gt;p&lt;/i&gt; = 0.00) when compared with non-sarcopenic and non-sarcopenic (other co-morbidities) group, respectively. CAF levels were also negatively associated with hand grip strength (HGS) and skeletal muscle index (SMI) with an effect size of 1.09 (ROM = 1.09 with 95% CI [1.05 to 1.13], &lt;i&gt;p&lt;/i&gt; = 0.00) and 1.10 (ROM = 1.10 with 95% CI [1.05 to 1.14], &lt;i&gt;p&lt;/i&gt; = 0.00), respectively. Meta-regression and subgroup analysis revealed that although sarcopenia is associated with increasing age, the correlation between CAF and age was statistically insignificant (&lt;i&gt;p&lt;/i&gt; = 0.44), suggesting that the variation of age among sarcopenia patients could be source of heterogeneity among studies. All the studies included in the meta-analysis reported low risk of bias.&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 meta-analysis concluded that elevated CAF levels were associated with sarcopenia and decreased HGS and SMI. CAF could serve as a valuable mark","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056955","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":"The Effect of Anti-Activin Receptor Type IIA and Type IIB Antibody on Muscle, Bone and Blood in Healthy and Osteosarcopenic Mice","authors":"Frederik Duch Bromer,&nbsp;Andreas Lodberg,&nbsp;Marco Eijken,&nbsp;Christian Brix Folsted Andersen,&nbsp;Mathias Flensted Poulsen,&nbsp;Jesper Skovhus Thomsen,&nbsp;Annemarie Brüel","doi":"10.1002/jcsm.13718","DOIUrl":"10.1002/jcsm.13718","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;Anti-Activin Receptor Type IIA and Type IIB antibody (αActRIIA/IIB ab) is a recently developed drug class that targets the activin receptor signalling pathway. Inhibition of receptor ligands (activins, myostatin, growth differentiation factor 11, etc.) can lead to skeletal muscle hypertrophy, bone formation, and increased haematopoiesis. Despite the αActRIIA/IIB ab, bimagrumab, having progressed to clinical trials, two crucial questions about αActRIIA/IIB ab therapy remain: Does αActRIIA/IIB ab influence bone metabolism and bone strength similarly to its generic classmates (activin receptor-based ligand traps)? Does αActRIIA/IIB ab affect red blood cell parameters, thereby increasing the risk of thromboembolism, similar to its generic classmates? Therefore, the aim of the present study was to investigate the therapeutic potential of αActRIIA/IIB ab in a mouse model of concurrent sarcopenia and osteopenia and to investigate the effect on bone and haematopoiesis in more detail.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In C57BL/6JRj mice, combined sarcopenia and osteopenia were induced locally by injecting botulinum toxin A into the right hindlimb, resulting in acute muscle paresis. Immediately after immobilization, mice received twice-weekly intraperitoneal injections with αActRIIA/IIB ab (10 mg/kg) for 21 days, after which they were sacrificed. Muscle mass, skeletal muscle fibre size and Smad2 expression were analysed in the rectus femoris and gastrocnemius muscles. Bone mass and bone microstructure were analysed in the trabecular bone at the distal femoral metaphysis, while the cortical bone was analysed at the femoral mid-diaphysis. In a substudy, the effect on haematopoiesis was explored 2 and 7 days after a single αActRIIA/IIB ab (30 mg/kg) injection in C57BL/6JRj mice.&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;αActRIIA/IIB ab caused a large increase in muscle mass in both healthy (+21%) and immobilized (sarcopenic and osteopenic) (+12%) mice. Furthermore, αActRIIA/IIB ab increased trabecular bone (bone volume fraction) for both healthy (+65%) and immobilized (+44%) mice. For cortical bone, αActRIIA/IIB ab caused a small, but significant, increase in bone area (+6%) for immobilized mice, but not for healthy mice. Treatment with αActRIIA/IIB ab did not change red blood cell count, haemoglobin concentration or mean cell volume after either 2 or 7 days.&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;Treatment with αActRIIA/IIB ab caused a significant increase in both skeletal muscle mass and bone ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056296","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":"Defective Cystic Fibrosis Transmembrane Conductance Regulator Accelerates Skeletal Muscle Aging by Impairing Autophagy/Myogenesis","authors":"Ziyi Chen,&nbsp;Jiankun Xu,&nbsp;Peijie Hu,&nbsp;Wanting Du,&nbsp;Junjiang Chen,&nbsp;Xiaotian Zhang,&nbsp;Wei Zhou,&nbsp;Jiayang Gao,&nbsp;Yuantao Zhang,&nbsp;Bingyang Dai,&nbsp;Guangshuai Nie,&nbsp;Jun Hu,&nbsp;Liangbin Zhou,&nbsp;Shunxiang Xu,&nbsp;Hisao Chang Chan,&nbsp;Wing-hoi Cheung,&nbsp;Ye Chun Ruan,&nbsp;Ling Qin","doi":"10.1002/jcsm.13708","DOIUrl":"10.1002/jcsm.13708","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Regenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Vastus lateralis biopsy samples from male and female human subjects (<i>n</i> = 23) of 7- to 86-year-old and gastrocnemii tissues from mice of 4- to 29-month-old were examined for CFTR expression. Skeletal muscle tissues or cultured myoblasts from mice carrying CFTR mutation (DF508) at 4- to 18-month-old were used for assessment of muscle mass, contractile force and regenerative capacity as well as myogenic and autophagy signalling. Overexpression of LC3-<i>β</i>, an autophagy mediator, was conducted to reverse myogenic defects in DF508 myoblasts. Adenoviruses containing CFTR gene or pharmaceuticals that enhance CFTR (VX809) were locally injected into the gastrocnemius or femoris quadricep to rescue age-related skeletal muscle defects in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>mRNA levels of CFTR in human vastus lateralis exhibited significantly negative correlations with age (<i>r</i> = −0.87 in males and −0.62 in females, <i>p</i> &lt; 0.05). Gastrocnemius mRNA level of CFTR decreased by 77.7 ± 4.6% in 29-month-old wild-type mice compared to the 4-month-old. At 18-month-old, DF508 mice showed significantly reduced lean mass (by 35.6%), lower specific twitch force of the gastrocnemius (by 46.2%), decrease in fast/slow-twitch muscle isoform ratio as well as downregulation of myogenic (e.g., MYOD and MYOG) or autophagy/mitophagy (e.g., LC3-<i>β</i>) genes, compared to age-matched wild-types. Post-injury gastrocnemius regeneration was found impaired in DF508 mice. Myoblast cultures from DF508 mice showed defective myogenic differentiation, which was reversed by overexpressing LC3-β. In aged (&gt; 15-month-old) mice, overexpressing CFTR or VX809 restored the expression of autophagy or myogenic genes, increased mitochondrial LC3-β level and improved skeletal muscle mass and function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Age-related reduction in skeletal muscle expression of CFTR impairs autophagy and myogenesis, exacerbating skeletal muscle aging. Enhancing CFTR might be a potential treatment strategy for age-related skeletal muscle disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056249","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":"PrPC Glycoprotein Is Indispensable for Maintenance of Skeletal Muscle Homeostasis During Aging","authors":"Wenduo Liu,&nbsp;Thi Thu Trang Kieu,&nbsp;Zilin Wang,&nbsp;Hyun-Jaung Sim,&nbsp;Seohyeong Lee,&nbsp;Jeong-Chae Lee,&nbsp;Yoonjung Park,&nbsp;Sang Hyun Kim,&nbsp;Sung-Ho Kook","doi":"10.1002/jcsm.13706","DOIUrl":"10.1002/jcsm.13706","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 cellular prion protein (PrP&lt;sup&gt;C&lt;/sup&gt;), a glycoprotein encoded by the &lt;i&gt;PRNP&lt;/i&gt; gene, is known to modulate muscle mass and exercise capacity. However, the role of PrP&lt;sup&gt;C&lt;/sup&gt; in the maintenance and regeneration of skeletal muscle during ageing remains unclear.&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 study investigated the change in PrP&lt;sup&gt;C&lt;/sup&gt; expression during muscle formation using C2C12 cells and evaluated muscle function in &lt;i&gt;Prnp&lt;/i&gt; wild-type (WT) and knock-out (KO) mice at different ages (1, 9 and 15 months). To determine the role of PrP&lt;sup&gt;C&lt;/sup&gt; in skeletal muscle homeostasis during ageing, we conducted regeneration experiments via cardiotoxin injection in &lt;i&gt;Prnp&lt;/i&gt; mice to assess the effects of PrP&lt;sup&gt;C&lt;/sup&gt; deficiency on the senescence of satellite stem cells (SCs) and regenerative capacity in skeletal muscle.&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;Our data demonstrate that PrP&lt;sup&gt;C&lt;/sup&gt; expression increased significantly during muscle differentiation (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), correlating with myogenin (immunofluorescence at the differentiation stage). PrP&lt;sup&gt;C&lt;/sup&gt; deficiency disrupted muscle homeostasis, leading to age-associated mitochondrial autophagy (Pink-1, +180%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; Parkin, +161%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and endoplasmic reticulum stress (SERCA, −26%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; IRE1&lt;i&gt;α&lt;/i&gt;, +195%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) while decreasing the level of mitochondrial biogenesis (SIRT-1, −50%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; PGC-1&lt;i&gt;α&lt;/i&gt;, −36%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; VDAC, −27%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and activated oxidative stress (serum myoglobin, +23%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; MDA, +23%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; NF&lt;i&gt;κ&lt;/i&gt;B, +117%, p &lt; 0.05) during ageing, which accelerated reduced muscle growth or mass accumulation (tibialis anterior muscle mass, −23%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; gastrocnemius muscle mass, −30%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; muscle fibre size, −48%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; MSTN, +160%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; MAFbx, +83%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Furthermore, PrP&lt;sup&gt;C&lt;/sup&gt; deficiency induced the senescence (&lt;i&gt;β&lt;/i&gt;-galactosidase, +60%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; p16, +103%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) of SCs, which was directly related to the defect in muscle recovery, with the senescence-mediated enhancement of adipogenesis (PPAR&lt;i&gt;γ&lt;/i&gt;, +74%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) during the regeneration process after cardiotoxin-induced muscle injury.&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 findings demonstrate that PrP&lt;sup&gt;C&lt;/sup&gt; is indispensable for maintaining skeletal muscle homeostas","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050824","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":"Aptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function","authors":"Jia Song,&nbsp;Mengmeng Yang,&nbsp;Longqing Xia,&nbsp;Liming Wang,&nbsp;Kewei Wang,&nbsp;Yingyue Xiang,&nbsp;Jun Cheng,&nbsp;Jun Chen,&nbsp;Jidong Liu,&nbsp;Ruxing Zhao,&nbsp;Fuqiang Liu,&nbsp;Zheng Sun,&nbsp;Xinguo Hou,&nbsp;Nan Zang,&nbsp;Li Chen","doi":"10.1002/jcsm.13717","DOIUrl":"10.1002/jcsm.13717","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;Muscle atrophy is associated with Type 2 diabetes mellitus, which reduces the quality of life and lacks effective treatment strategies. Previously, it was determined that human umbilical cord mesenchymal stromal cell (hucMSC)–derived exosomes (EXOs) ameliorate diabetes-induced muscle atrophy. However, the systemic application of EXOs is less selective for diseased tissues, which reduces their efficacy and safety associated with their nonspecific biological distribution in vivo. Therefore, improving exosomal targeting is imperative. In this study, a skeletal muscle–specific aptamer (Apt) was used to explore the effects of Apt-functionalized EXOs derived from hucMSCs in diabetes-associated muscle atrophy and its specific mechanisms.&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;Diabetic db/db mice and C2C12 myotubes were used to explore the effects of MSC-EXOs or Apt-EXOs in alleviating muscle atrophy. Grip strength, muscle weight and muscle fibre cross-sectional area (CSA) were used to evaluate skeletal muscle strength and muscle mass. Western blot analysis of muscle atrophy signalling, including MuRF1 and Atrogin 1 and the mitochondrial complex and Seahorse analysis were performed to investigate the underlying mechanisms of MSC-EXOs or Apt-EXOs on muscle atrophy.&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;MSC-EXOs increased grip strength (&lt;i&gt;p&lt;/i&gt; = 0.0002) and muscle mass (&lt;i&gt;p&lt;/i&gt; = 0.0044 for tibialis anterior (TA) muscle, &lt;i&gt;p&lt;/i&gt; = 0.002 for soleus (SO) muscle) in db/db mice. It also increased the CSA of muscle fibres (&lt;i&gt;p&lt;/i&gt; = 0.0011 for all fibres, &lt;i&gt;p&lt;/i&gt; = 0.0036 for slow muscle fibres and &lt;i&gt;p&lt;/i&gt; = 0.0089 for fast muscle fibres) and the percentage of slow-to-fast muscle fibres (&lt;i&gt;p&lt;/i&gt; = 0.0109). However, Atrogin 1 (&lt;i&gt;p&lt;/i&gt; = 0.0455) and MuRF1 expression (&lt;i&gt;p&lt;/i&gt; = 0.0168) was reduced. MSC-EXOs activated SIRT1/FoxO1/3a signalling and enhanced mitochondrial function in db/db mice and C2C12 myotubes. SIRT1 knockdown decreased the beneficial antiatrophic effects of MSC-EXOs. Additionally, Apt conjugation increased the effect of MSC-EXOs on muscle atrophy and myofiber-type transition (&lt;i&gt;p&lt;/i&gt; = 0.0133 for grip strength, &lt;i&gt;p&lt;/i&gt; = 0.0124 for TA muscle weight, &lt;i&gt;p&lt;/i&gt; = 0.0008 for SO muscle weight, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 for CSA of all muscle fibres, &lt;i&gt;p&lt;/i&gt; = 0.0198 for CSA of slow muscle fibres, &lt;i&gt;p&lt;/i&gt; = 0.0213 for CSA of fast muscle fibres, &lt;i&gt;p&lt;/i&gt; = 0.011 for percentage of slow–fast muscle fibres, &lt;i&gt;p&lt;/i&gt; = 0.0141 for Atrogin 1 expression and &lt;i&gt;p&lt;/i&gt; = 0.005 for MuRF1 expression).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050823","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}