Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"The Innovative Role of Nuclear Receptor Interaction Protein in Orchestrating Invadosome Formation for Myoblast Fusion","authors":"Hsin-Hsiung Chen, Chia-Yang Lin, Ya-Ju Han, Yun-Hsin Huang, Yi-Hsiang Liu, Wan-En Hsu, Li-Kai Tsai, Hsing-Jung Lai, Yeou-Ping Tsao, Hsiang-Po Huang, Show-Li Chen","doi":"10.1002/jcsm.13598","DOIUrl":"https://doi.org/10.1002/jcsm.13598","url":null,"abstract":"Nuclear receptor interaction protein (NRIP) is versatile and engages with various proteins to execute its diverse biological function. NRIP deficiency was reported to cause small myofibre size in adult muscle regeneration, indicating a crucial role of NRIP in myoblast fusion.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"35 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321859","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":"LRRK2^G2019S Gene Mutation Causes Skeletal Muscle Impairment in Animal Model of Parkinson's Disease.","authors":"Yiying Hu, Huijia Yang, Chunli Song, Lulu Tian, Panpan Wang, Tianbai Li, Cheng Cheng, Murad AlNusaif, Song Li, Zhanhua Liang, Weidong Le","doi":"10.1002/jcsm.13604","DOIUrl":"https://doi.org/10.1002/jcsm.13604","url":null,"abstract":"<p><strong>Background: </strong>While the gradually aggravated motor and non-motor disorders of Parkinson's disease (PD) lead to progressive disability and frequent falling, skeletal muscle impairment may contribute to this condition. The leucine-rich repeat kinase2 (LRRK2) is a common disease-causing gene in PD. Little is known about its role in skeletal muscle impairment and its underlying mechanisms.</p><p><strong>Methods: </strong>To investigate whether the mutation in LRRK2 causes skeletal muscle impairment, we used 3-month-old (3mo) and 14-month-old (14mo) LRRK2^G2019S transgenic (TG) mice as a model of PD, compared with the age-matched littermate wild-type (WT) controls. We measured the muscle mass and strength, ultrastructure, inflammatory infiltration, mitochondrial morphology and dynamics dysfunction through behavioural analysis, electromyography (EMG), immunostaining, transmission electron microscopy (TEM) and other molecular biology techniques.</p><p><strong>Results: </strong>The 3mo-TG mice display mild skeletal muscle impairment with spontaneous potentials in EMG (increased by 130%, p < 0.05), myofibre necrosis (p < 0.05) and myosin heavy chain-II changes (reduced by 19%, p < 0.01). The inflammatory cells and macrophage infiltration are significantly increased (CD8a⁺ and CD68⁺ cells up 1060% and 579%, respectively, both p < 0.0001) compared with the WT mice. All of the above pathogenic processes are aggravated by aging. The 14mo-TG mice EMG examinations show a reduced duration (by 31%, p < 0.01) and increased polyphasic waves of motor unit action potentials (by 28%, p < 0.05). The 14mo-TG mice present motor behavioural deficits (p < 0.05), muscle strength and mass reduction by 37% and 8% (p < 0.05 and p < 0.01, respectively). A remarkable increase in inflammatory infiltration is accompanied by pro-inflammatory cytokines in the skeletal muscles. TEM analysis shows muscle fibre regeneration with the reduced length of sarcomeres (by 6%;p < 0.05). The muscle regeneration is activated as Pax7⁺ cells increased by 106% (p < 0.0001), andmyoblast determination protein elevated by 71% (p < 0.01). We also document the morphological changes and dynamics dysfunction of mitochondria with the increase of mitofusin1 by 43% (p < 0.05) and voltage-dependent anion channel 1 by 115% (p < 0.001) in the skeletal muscles of 14mo-TG mice.</p><p><strong>Conclusions: </strong>Taken together, these findings may provide new insights into the clinical and pathogenic involvement of LRRK2^G2019 mutation in muscles, suggesting that the diseases may affect not only midbrain dopaminergic neurons, but also other tissues, and it may help overall clinical management of this devastating disease.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277667","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":"Sarcopenia interventions in long-term care facilities targeting sedentary behaviour and physical inactivity: A systematic review.","authors":"Yihan Mo,Linghui Chen,Yuxin Zhou,Anna Bone,Matthew Maddocks,Catherine J Evans","doi":"10.1002/jcsm.13576","DOIUrl":"https://doi.org/10.1002/jcsm.13576","url":null,"abstract":"BACKGROUNDSedentary behaviour and physical inactivity are independent risk factors for sarcopenia for long-term care facility residents. Understanding the components, mechanisms and context of interventions that target change in these risk factors can help optimize sarcopenia management approaches. This study aimed to identify, appraise and synthesize the interventions targeting sedentary behaviour and physical inactivity, construct a Theory of Change logic model, inform complex sarcopenia intervention development and identify areas for improvement.METHODSEight electronic databases, including Embase and Web of Science, were searched for eligible interventional studies from inception until February 2024. Narrative synthesis was used. The Theory of Change was applied to develop a logic model presenting the synthesized results. A Cochrane risk of bias assessment tool was used for quality appraisal.RESULTSThe study included 21 articles involving 1014 participants, with mean ages ranging from 72.5 to 90.4 years. The proportion of female participants ranged from 8.0% to 100.0%. The applied sarcopenia diagnosis criteria varied, including those of the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People. The overall risk of bias in the included studies was moderate. Interventions primarily targeted physical inactivity, with resistance training being the most common intervention type. The reporting of intervention adherence was insufficient (only 11 out of 21 included studies provided adherence reports), and adherence overall and by intervention type was not possible to discern due to inconsistent criteria for high adherence across these studies. Four categories of intervention input were identified: educational resources; exercise equipment and accessories; monitoring and tailoring tools; and motivational strategies. Intervention activities fell into five categories: determining the intervention plan; educating; tailoring; organizing, supervising, assisting and motivating; and monitoring. While sarcopenia-related indicators were commonly used as desired outcomes, intermediate outcomes (i.e., sedentary time and physical activity level) and other long-term outcomes (i.e., economic outcomes) were less considered. Contextual factors affecting intervention use included participant characteristics (i.e., medical condition and education level) and intervention provider characteristics (i.e., trustworthiness).CONCLUSIONSThe findings led to the development of a novel logic model detailing essential components for interventions aimed at managing sarcopenia in long-term care facilities, with a focus on addressing sedentary behaviour and physical inactivity. Future sarcopenia interventions in long-term care facilities should fully attend to sedentary behaviour, enhance adherence to interventions through improved education, monitoring, tailoring and motivation and establish an agreed standard set of outcome measures.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"2 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245390","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":"Frequency of weight and body composition increases in advanced non-small cell lung cancer patients during first line therapy.","authors":"Philip Bonomi,Hita Moudgalya,Sandra L Gomez,Palmi Shah,Sanjib Basu,Marta Batus,Levi B Martinka,Ahmed Abdelkader,Iphigenia Tzameli,Sonia Cobain,Susie Collins,Edmund J Keliher,Danna M Breen,Roberto A Calle,Mary Jo Fidler,Jeffrey A Borgia","doi":"10.1002/jcsm.13534","DOIUrl":"https://doi.org/10.1002/jcsm.13534","url":null,"abstract":"BACKGROUNDThe primary objective of this study was to assess the frequency of body composition increases and their relationships to changes in body weight in two cohorts of real world, treatment-naïve, advanced non-small cell lung cancer (NSCLC) patients. One cohort received the current standard of care (CSOC), which consisted of immunotherapy and newer chemotherapy regimens, and the other cohort was treated with the former standard of care (FSOC), consisting only of older platinum-containing regimens.METHODSCSOC (n = 106) and FSOC (n = 88) cohorts of advanced NSCLC patients were included in this study. Weights were collected at each clinical visit, and body composition analysis from routine chest computed tomography via automated segmentation software assessed at baseline and at 6 and 12 weeks. Standard statistical methods were used to calculate relationships between changes in weight and in body composition.RESULTSThe CSOC cohort contained 106 stage IV NSCLC patients treated between 16/12/2014 and 22/10/2020 while the FSOC cohort contained 88 stage III/IV NSCLC patients treated between 16/6/2006 and 18/11/2014. While each cohort exhibited decreases in median weight, body mass index (BMI), mean skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at the 6 and 12 week time points, a subset of patients experienced increases in these parameters. Using a threshold of ≥2.5% increase for weight, BMI, SMI, and SATI at the 12 week time point, both cohorts showed similar (20.5% and 27.3%) increases in these parameters. With a cut point of ≥5% increase at 12 weeks follow-up, 8.0% to 25.0% of the patients gained ≥5% in weight, BMI, SMI and SATI. Comparing these results in each cohort showed no significant differences. Pearson coefficients for weight change related to changes in SMI and SATI at 6 and 12 weeks ranged from 0.31 to 0.58 with all P values <0.02. Pearson coefficients for weight change at 12 weeks related to changes in VATI and IMATI ranged from 0.26 to 0.47 with all P values <0.05. Comparison of Pearson coefficients for each cohort showed no significant differences.CONCLUSIONSAlthough decreases in median weight, BMI, SMI and SATI were observed in both cohorts, similar percentage of patients in each cohort experienced increases in these parameters. These findings, plus the positive correlations between longitudinal measurements of weight, muscle mass and adipose tissue, indicate that weight gain in these patients involves increases in both muscle mass and adipose tissue. Upon validation, these findings could have implications for clinical trial design and for translational research in cancer cachexia.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"50 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245398","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":"Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle","authors":"Samuel O. Lord, Harvey E. Johnston, Rahul S. Samant, Yu-Chiang Lai","doi":"10.1002/jcsm.13601","DOIUrl":"https://doi.org/10.1002/jcsm.13601","url":null,"abstract":"Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal muscle in overall health is widely acknowledged, unravelling the underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, a crucial post-translational modification, is involved in regulating most biological processes. This widespread impact is achieved through a diverse set of enzymes capable of generating structurally and functionally distinct ubiquitin modifications on proteins. The complexity of protein ubiquitylation has presented significant challenges in not only identifying ubiquitylated proteins but also characterising their functional significance. Mass spectrometry enables in-depth analysis of proteins and their post-translational modification status, offering a powerful tool for studying protein ubiquitylation and its biological diversity: an approach termed ubiquitylomics. Ubiquitylomics has been employed to tackle different perspectives of ubiquitylation, including but not limited to global quantification of substrates and ubiquitin linkages, ubiquitin site recognition and crosstalk with other post-translational modifications. As the field of mass spectrometry continues to evolve, the usage of ubiquitylomics has unravelled novel insights into the regulatory mechanisms of protein ubiquitylation governing biology. However, ubiquitylomics research has predominantly been conducted in cellular models, limiting our understanding of ubiquitin signalling events driving skeletal muscle biology. By integrating the intricate landscape of protein ubiquitylation with dynamic shifts in muscle physiology, ubiquitylomics promises to not only deepen our understanding of skeletal muscle biology but also lay the foundation for developing transformative muscle-related therapeutics. This review aims to articulate how ubiquitylomics can be utilised by researchers to address different aspects of ubiquitylation signalling in skeletal muscle. We explore methods used in ubiquitylomics experiments, highlight relevant literature employing ubiquitylomics in the context of skeletal muscle and outline considerations for experimental design.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"12 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234097","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":"Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis","authors":"Yueyuan Zhou, Limei Kang, Geng Yin, Leiyi Yang, Bo Chen, Binhan Liu, Xiaoyan Zhu, Qibing Xie","doi":"10.1002/jcsm.13581","DOIUrl":"https://doi.org/10.1002/jcsm.13581","url":null,"abstract":"Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM).","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"22 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235533","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":"High‐Intensity Interval Training Mitigates Sarcopenia and Suppresses the Myoblast Senescence Regulator EEF1E1","authors":"Yaoshan Dun, Wenliang Zhang, Yang Du, Kangling Xie, Yuan Liu, Cui Li, Ling Qiu, Siqian Fu, Thomas P. Olson, Yuqiong Long, Baiyang You, Suixin Liu","doi":"10.1002/jcsm.13600","DOIUrl":"https://doi.org/10.1002/jcsm.13600","url":null,"abstract":"BackgroundThe optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia.MethodsWe conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; &lt;jats:italic&gt;n&lt;/jats:italic&gt; = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53.ResultsThe crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, &lt;jats:italic&gt;p&lt;/jats:italic&gt; = 0.03) and was associated with skeletal muscle index (&lt;jats:italic&gt;R&lt;/jats:italic&gt;&lt;jats:sup&gt;2&lt;/jats:sup&gt; = 0.51, &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.001) and hand grip strength (&lt;jats:italic&gt;R&lt;/jats:italic&gt;&lt;jats:sup&gt;2&lt;/jats:sup&gt; = 0.54, &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.05). HIIT reduced EEF1E1 expression and mitigated age‐related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D‐galactose‐induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all &lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process (&lt;jats:italic&gt;p&lt;/jats:italic&gt; &lt; 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"27 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231206","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":"Novel insights into the association between genetically proxied inhibition of proprotein convertase subtilisin/kexin type 9 and risk of sarcopenia","authors":"Hongyan Jiang, Lulu Li, Xue Zhang, Jia He, Chuanhuai Chen, Ruimin Sun, Ying Chen, Lijuan Xia, Lei Wen, Yunxiang Chen, Junxiu Liu, Lijiang Zhang, Wanqiang Lv","doi":"10.1002/jcsm.13575","DOIUrl":"https://doi.org/10.1002/jcsm.13575","url":null,"abstract":"The effects of lipid-lowering drugs [including statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors] on hyperlipidaemia have been established. Some may have treatment effects beyond their reported properties, offering potential opportunities for drug repurposing. Epidemiological studies have reported conflicting findings on the relationship between lipid-lowering medication use and sarcopenia risk.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"49 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160925","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":"Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice.","authors":"Wilbert P Vermeij, Khalid Alyodawi, Ivar van Galen, Jennie L von der Heide, María B Birkisdóttir, Lisanne J Van't Sant, Rutger A Ozinga, Daphne S J Komninos, Kimberly Smit, Yvonne M A Rijksen, Renata M C Brandt, Sander Barnhoorn, Dick Jaarsma, Sathivel Vaiyapuri, Olli Ritvos, Tobias B Huber, Oliver Kretz, Ketan Patel","doi":"10.1002/jcsm.13570","DOIUrl":"https://doi.org/10.1002/jcsm.13570","url":null,"abstract":"<p><strong>Background: </strong>Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well-established long-term intervention recognized for its universal anti-ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair-deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity.</p><p><strong>Methods: </strong>Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1^Δ/- progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney.</p><p><strong>Results: </strong>Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P < 0.001), with sActRIIB clearly increasing muscle mass (35-65%) and tetanic force (P < 0.001). The combined regime yielded a stable uniform body weight, but increased compared with DR alone, synergistically improved motor coordination and further delayed the onset and development of balance problems. sActRIIB significantly increased muscle fibre size (P < 0.05) in mice subjected to DR and lowered all signs of muscle damage. Ercc1^Δ/- mice showed abnormal neuromuscular junctions. Single interventions by sActRIIB treatment or DR only partially rescued this phenotype, while in the double intervention group, the regularly shaped junctional foldings were maintained. In kidney of Ercc1^Δ/- mice, we observed a mild but significant foot process effacement, which was restored by either intervention. Transcriptome analysis also pointed towards reduced levels of DNA damage in muscle and kidney by DR, but not sActRIIB, while these levels retained lower in the double intervention.</p><p><strong>Conclusions: </strong>In muscle, we found synergistic effects of combining sActRIIB with DR, but not in kidney, with an overall better health in the double intervention group. Crucially, the benefits of each single intervention are not lost when administered in combination, but rather strengthened, even when sActRIIB was applied late in life, opening opportunities for translation to human.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152725","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":"Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.","authors":"Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young-Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee","doi":"10.1002/jcsm.13582","DOIUrl":"https://doi.org/10.1002/jcsm.13582","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics.</p><p><strong>Methods: </strong>After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort.</p><p><strong>Results: </strong>Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799).</p><p><strong>Conclusions: </strong>SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124373","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}