Skeletal Muscle最新文献

{"title":"Caloric restriction reprograms skeletal muscle molecular pathways in non-human primates: potential relevance to human aging biology.","authors":"Jayanta Kumar Das, Nirad Banskota, Stefano Donega, Nader Shehadeh, Yulan Piao, Nathan Price, Julie A Mattison, Julián Candia, Rafael de Cabo, Luigi Ferrucci","doi":"10.1186/s13395-026-00422-9","DOIUrl":"https://doi.org/10.1186/s13395-026-00422-9","url":null,"abstract":"<p><strong>Background: </strong>Caloric restriction (CR), achieved by reducing energy intake without malnutrition, has been shown to preserve muscle function and delay age-related declines in strength and mobility by modulating key metabolic and molecular pathways involved in muscle maintenance. While most initial research on CR was done in rodents, non-human primates (NHPs) offer a higher translatable animal model for understanding CR effects due to their close genetic, physiological and cognitive similarities to humans.</p><p><strong>Methods: </strong>In this cross-sectional study, we investigated skeletal muscle gene expression changes induced by 30% CR in skeletal muscle in rhesus monkeys (n = 18 CR, n = 18 control). We performed high-depth RNA sequencing to profile gene expression and alternative splicing variants and identify pathways linked to aging, regeneration/degeneration, and energy metabolism.</p><p><strong>Results: </strong>Transcriptomic profiling revealed widespread gene expression differences between CR animals compared to controls. Genes that were overexpressed were mainly involved in pathways related to energy metabolism, mitochondrial function, signaling, and oxidative stress response. Conversely, underexpressed genes were connected to immune response, extracellular matrix organization, apoptosis, and ribosomal RNA processing. Further, we identify alternative splicing as a major mechanism by which CR modulates genes involved in muscle function, metabolism, and aging.</p><p><strong>Conclusions: </strong>Caloric restriction preserves skeletal muscle by enhancing metabolism, limiting degeneration and inflammation, and engaging conserved mechanisms across species.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence dynamics define therapeutic windows for Duchenne muscular dystrophy in DBA/2-mdx mice.","authors":"Aina Calls-Cobos, Aida Beà Tàrrega, Andrés Cisneros, Megan Rommelfanger, Silvia Campanario, Mercedes Grima-Terrén, Ignacio Ramírez-Pardo, Victoria Moiseeva, Vera Lukesova, Eva Andrés, Grace Chou, Yuewen Zheng, Nasun Hah, Albert Blasco-Roset, Ana Planavila, Carolina Soler-Botija, Antoni Bayés-Genís, Eusebio Perdiguero, Antonio L Serrano, Pura Muñoz-Cánoves","doi":"10.1186/s13395-026-00426-5","DOIUrl":"https://doi.org/10.1186/s13395-026-00426-5","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a severe X-linked disorder marked by progressive muscle degeneration and regeneration, inflammation and fibrosis. Cellular senescence has emerged as a potential driver of chronic muscle damage, yet its temporal dynamics and therapeutic relevance remain unclear.</p><p><strong>Methods: </strong>We analyzed senescent cell burden in skeletal and cardiac muscles of the DBA/2-mdx mouse model, which closely mimics features of human DMD. The senolytic combination of dasatinib and quercetin (D + Q) was administered during early or late disease phases to evaluate the impact of senescent cell clearance. Skeletal muscle strength was measured by grip strength and ex vivo force assays, while cardiac function was assessed by echocardiography. Fibrosis and senescence markers were quantified histologically, and transcriptional changes associated with senolysis were identified using bulk RNA sequencing (RNA-seq).</p><p><strong>Results: </strong>In skeletal muscle, senescent cells appear and peak during early stages of disease progression (3-5 months), coinciding with high degeneration and regeneration activity, and then decline with age as fibrosis increases. In contrast, in the heart, senescent cells emerge at late stages of disease progression (around 12 months), correlating with heart fibrogenesis. Notably, senolytic intervention in the DBA/2-mdx mice promotes a regenerative and antifibrotic gene signature in both tissues. However, the timing of senolytic therapy determines its efficacy: early treatment with D + Q reduces senescent cell burden, decreases fibrosis, and improves fiber size and contractile performance in skeletal muscle, while later treatment reduces cardiac senescence and fibrosis but does not improve skeletal muscle pathology.</p><p><strong>Conclusions: </strong>Cellular senescence is a dynamic and targetable feature in DMD, with tissue- and age-specific patterns. It represents a potential modifiable therapeutic target, and temporally optimized senolytic strategies could serve as effective adjuncts to current and emerging DMD treatments.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-derived skeletal muscle spheroids for Duchenne Muscular Dystrophy modeling.","authors":"Joyce Esposito, Felipe de Souza Leite, Igor Neves Barbosa, Thaís Maria da Mata Martins, Giovanna Gonçalves de Oliveira Olberg, Ziad Al Tanoury, Kayque Alves Telles-Silva, Mayana Cristina da Silva Pardo, Tatiana Jazedje, Raul Hernandes Bortolin, Mario Hiroyuki Hirata, Olivier Pourquié, Mayana Zatz","doi":"10.1186/s13395-026-00428-3","DOIUrl":"https://doi.org/10.1186/s13395-026-00428-3","url":null,"abstract":"<p><strong>Background: </strong>The progressive skeletal muscle degeneration observed in Duchenne Muscular Dystrophy (DMD) patients requires multiple cycles of satellite cells (SCs) activation to promote tissue regeneration. Dystrophic SCs present intrinsic defects, and the disrupting fibrotic niche hinders appropriate muscle recovery. Traditional 2D culture systems face challenges in modeling the DMD muscle niche and SCs behavior. Our aim was to validate a 3D culture of skeletal muscle spheroids (iSMS) for DMD modeling, as compared to the traditional 2D culture, while investigating the pathophysiological mechanisms of dystrophin deficiency in vitro.</p><p><strong>Methods: </strong>To compare iSMS with traditional 2D myogenic differentiation, we differentiated wild-type (WT), dystrophic (DMD) isogenic induced pluripotent stem cells (iPSCs), as well as iPSCs derived from DMD patients, characterized myogenic markers levels and assessed differences in proliferation and differentiation using RT-qPCR, immunofluorescence, and flow cytometry.</p><p><strong>Results: </strong>Our data showed that iSMS improved PAX7 expression in vitro, while MYOD1, MYOG, MYF5, and MYH3 expression were significantly reduced. These findings suggest that, at three weeks of myogenic differentiation, iSMS cultures retained satellite-like cells in a less activated, progenitor-like state. Accordingly, we identified higher expression of canonical Notch signaling genes such as JAG1 and NOTCH1 in iSMS compared to 2D. We also characterized the response of 2D and iSMS to terminal differentiation medium, providing a valuable comparison with muscle fibers derived from human adult myoblasts. Additionally, we showed that DMD iSMS-derived progenitors proliferated at reduced levels compared with WT, a characteristic not observed in progenitors derived from 2D cultures. Finally, we performed iSMS and 2D myogenic differentiation of iPSC lines from three patients with DMD.</p><p><strong>Conclusion: </strong>Our results highlight important advantages of using the iSMS differentiation platform over 2D for DMD in vitro modeling. Exploring these 3D systems may help to gain a deeper understanding of SCs behavior to advance in novel treatments for DMD, which might be applicable to other forms of muscular disorders.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulation of EGFR signaling in fibro-adipogenic precursors decreases adipogenesis in Duchenne muscular dystrophy.","authors":"Jules Guillemaud, Georgiana Panci, Aurélie Fessard, Léa Delivry, William Jarassier, Rémi Mounier, Julien Gondin, Stéphanie Gobert, Bénédicte Chazaud","doi":"10.1186/s13395-026-00429-2","DOIUrl":"https://doi.org/10.1186/s13395-026-00429-2","url":null,"abstract":"<p><strong>Background: </strong>Duchenne Muscular Dystrophy (DMD) is characterized by the formation of fibrosis and fat deposits that progressively replace muscle fibers, resulting in the loss of muscle function. Both fibrosis and adipogenesis are operated by fibroadipogenic precursors (FAPs), but the molecular regulation and interactions between the two processes are not fully understood.</p><p><strong>Methods: </strong>Adipogenesis was investigated in vivo in the D2-mdx mouse, and in vitro using FAPs isolated from WT (DBA/2) and D2-mdx muscles. Epithelial Growth Factor (EGF) was overexpressed in the D2-mdx muscle via electroporation of an expression plasmid.</p><p><strong>Results: </strong>We found that the D2-mdx gastrocnemius muscle showed fat deposition from 10 weeks of age and increased until 18 weeks of age, coinciding with fibrosis. Fat deposition was exclusively found within fibrotic areas. In vitro, D2-mdx FAPs proliferated more, and were more prone to adipogenesis than WT FAPs. Cells from both genotypes showed equal fibrogenesis. Analysis of normal muscle snRNAseq data showed that the Epithelial Growth Factor Receptor (EGFR) was primarily expressed by FAPs. Both EGFR expression and EGFR-phosphorylation were decreased in D2-mdx FAPs as compared with WT FAPs. Stimulating FAPs with EGF decreased adipogenesis, more efficiently in D2-mdx FAPs than in WT FAPs. However, EGF stimulation of EGFR had no effect on their fibrogenic differentiation. Finally, in vivo overexpression of EGF in D2-mdx gastrocnemius muscles reduced both adipogenesis and fibrosis, and was associated with an increased muscle force.</p><p><strong>Conclusions: </strong>In a DMD context, FAPs are more likely to differentiate into adipocytes than in normal muscle, which is associated with decreased EGFR signaling. Stimulating EGFR signaling decreased adipogenesis in vitro and fat deposition in vivo. The impact of EGFR signaling on fibrogenesis is unclear, the reduced fibrosis observed in vivo may be due to indirect mechanisms. This study identifies EGFR signaling as a new molecular mechanism for controlling adipogenesis in skeletal muscle FAPs.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanobiological landscape of muscle stem cells.","authors":"Kotaro Hirano, Yuji Hara","doi":"10.1186/s13395-026-00425-6","DOIUrl":"https://doi.org/10.1186/s13395-026-00425-6","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D skeletal muscle system for disease modelling and secretome profiling of Duchenne muscular dystrophy.","authors":"Mariam Zouhair, Marianna Cosentino, Ludovica Apa, Desiree Genovese, Sasha Marco Maria Di Iorio, Carmine Nicoletti, Domenico Liguoro, Giorgia Nanni, Simone Dinarelli, Alessandro Palma, Caterina Boccia, Laura Forcina, Silvia Sideri, Rita Mancini, Monica Ballarino, Antonio Musarò","doi":"10.1186/s13395-026-00423-8","DOIUrl":"https://doi.org/10.1186/s13395-026-00423-8","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pax7::Foxo1 conditional mouse strain.","authors":"G Roger Askew, Jonathan Gauntlett, Katherine Brechun, Harald Kranz, Nicholas Salters, Jess D Tate, Ellen Wang, Cassie Badger, Shireen Elhabian, Jared Schnider, Gillian St John, Samuel V Rasmussen, Narendra Bharathy, Charles Keller","doi":"10.1186/s13395-026-00424-7","DOIUrl":"10.1186/s13395-026-00424-7","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CtBP1 sustains activity-dependent muscle properties and dampens synaptic, contractile and metabolic changes triggered by denervation.","authors":"Olivia Cattaneo, Gaetan Lopez, Jayasimman Rajendran, Florent Chabry, Nicolas Liaudet, Sergei Startchik, Alexandre Prola, Perrine Castets","doi":"10.1186/s13395-026-00421-w","DOIUrl":"10.1186/s13395-026-00421-w","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin αVβ5 regulates myoblast proliferation and differentiation in sarcopenia mice treated with FNDC5 gene delivery : Original article.","authors":"Guoxi Gao, Qiyang Wang, Yuqiong Zhang, Minghong Shao, Yiming Liang, Shumin Zhou, Sheng Lu","doi":"10.1186/s13395-026-00420-x","DOIUrl":"https://doi.org/10.1186/s13395-026-00420-x","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional and structural pathologies in skeletal muscle of a rat model of Duchenne muscular dystrophy.","authors":"Young Il Lee, Cora C Hart, C Spencer Henley-Beasley, Jeffrey S Herr, Eli Zerpa, Elisabeth R Barton, David W Hammers, H Lee Sweeney","doi":"10.1186/s13395-026-00419-4","DOIUrl":"10.1186/s13395-026-00419-4","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a lethal pediatric degenerative muscle disease for which there is no cure. Robust preclinical models that recapitulate major clinical features of DMD are required to investigate efficacy of potential DMD therapeutics. Rat models of DMD have emerged as promising small animal models to accomplish this; however, there have been no comprehensive studies investigating the functional skeletal muscle decrements associated with the modeling of DMD in rats.</p><p><strong>Methods: </strong>CRISPR/Cas9 gene editing was used to generate a dystrophin-deficient Sprague-Dawley muscular dystrophy rat (MDR). Biochemical and immunofluorescent analyses were performed to confirm loss of dystrophin in striated muscles of this rat model. In situ and ex vivo muscle function was assessed in wild-type (WT) and MDR muscles at 3, 6, and 12 months of age, followed by histopathological analyses.</p><p><strong>Results: </strong>MDR muscle tissues exhibited loss of full-length dystrophin and reduced content of other dystrophin glycoprotein complex members. MDR extensor digitorum longus (EDL) muscles and diaphragms displayed pronounced and progressive muscle weakness beginning at 3 months of age, compared to WT littermates. EDLs also exhibit susceptibility to eccentric contraction-induced damage. Functional deficits in soleus muscles were less severe and were associated with a right shift in force-frequency relationship. MDR muscles display progressive histopathology including degenerative lesions, fibrosis, regenerative foci, and modest adipose deposition.</p><p><strong>Conclusions: </strong>MDR is a preclinical model of DMD that exhibits many translational features of the human disease, including a large dynamic range of muscle decrements, that has high utility for the evaluation of potential therapeutics for DMD.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}