{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T21:31:33Z","timestamp":1763415093725,"version":"3.41.2"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["NCN 2018\/29\/B\/NZ7\/02094"],"award-info":[{"award-number":["NCN 2018\/29\/B\/NZ7\/02094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The musculoskeletal system is one of the most affected organs by aging that correlates well with an accumulation of senescent cells as for other multiple age-related pathologies. The molecular mechanisms underpinning muscle impairment because of senescent cells are still elusive. The availability of in vitro model of skeletal muscle senescence is limited and restricted to a small panel of phenotypic features of these senescent cells in vivo. Here, we developed a new in vitro model of senescent C2C12 mouse myoblasts that, when subjected to differentiation, the resulting myotubes showed sarcopenic features. To induce senescence, we used SYUIQ-5, a quindoline derivative molecule inhibitor of telomerase activity, leading to the expression of several senescent hallmarks in treated myoblasts. They had increased levels of p21 protein accordingly with the observed cell cycle arrest. Furthermore, they had enhanced SA-\u03b2galactosidase enzyme activity and phosphorylation of p53 and histone H2AX. SYUIQ-5 senescent myoblasts had impaired differentiation potential and the resulting myotubes showed increased levels of ATROGIN-1 and MURF1, ubiquitin ligases components responsible for protein degradation, and decreased mitochondria content, typical features of sarcopenic muscles. Myotubes differentiated from senescent myoblasts cultures release increased levels of MYOSTATIN that could affect skeletal muscle cell growth. Overall, our data suggest that a greater burden of senescent muscle cells could contribute to sarcopenia. This study presents a well-defined in vitro model of muscle cell senescence useful for deeper investigation in the aging research field to discover new putative therapeutic targets and senescence biomarkers associated with the aged musculoskeletal system.<\/jats:p>","DOI":"10.1093\/gerona\/glae022","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T03:03:42Z","timestamp":1706151822000},"source":"Crossref","is-referenced-by-count":2,"title":["Murine Myoblasts Exposed to SYUIQ-5 Acquire Senescence Phenotype and Differentiate into Sarcopenic-Like Myotubes, an In Vitro Study"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-5328","authenticated-orcid":false,"given":"Laura","family":"Gerosa","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir Mohammad","family":"Malvandi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Gomarasca","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Verdelli","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Sansoni","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Faraldi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Ziemann","sequence":"additional","affiliation":[{"name":"Department of Athletics, Strength and Conditioning, Pozna\u0144 University of Physical Education , Pozna\u0144 , Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-1144","authenticated-orcid":false,"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, IRCCS INRCA , Ancona , Italy"},{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche , Ancona , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Banfi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University , Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-985X","authenticated-orcid":false,"given":"Giovanni","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi , Milano , Italy"},{"name":"Department of Athletics, Strength and Conditioning, Pozna\u0144 University of Physical Education , Pozna\u0144 , Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"2024040309525123700_CIT0001","first-page":"129","article-title":"An overview of sarcopenia: Facts and numbers on prevalence and clinical impact","volume-title":"J Cachexia Sarcopenia Muscle","author":"von Haehling","year":"2010"},{"key":"2024040309525123700_CIT0002","first-page":"249","article-title":"Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International working group on sarcopenia","volume-title":"J Am Med Dir Assoc.","author":"Fielding","year":"2011"},{"key":"2024040309525123700_CIT0003","first-page":"101943","article-title":"Exploring cellular senescence in the musculoskeletal system: Any insights for biomarkers discovery","volume-title":"Ageing Res Rev.","author":"Gerosa","year":"2023"},{"key":"2024040309525123700_CIT0004","first-page":"232","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume-title":"Nature.","author":"Baker","year":"2011"},{"key":"2024040309525123700_CIT0005","first-page":"585","article-title":"The serial cultivation of human diploid cell strains","volume-title":"Exp Cell Res.","author":"Hayflick","year":"1961"},{"key":"2024040309525123700_CIT0006","first-page":"e9188","article-title":"A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen","volume-title":"PLoS 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Physiol.","author":"Bilodeau","year":"2016"},{"key":"2024040309525123700_CIT0042","first-page":"501","article-title":"Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism","volume-title":"J Cell Physiol.","author":"McFarlane","year":"2006"},{"key":"2024040309525123700_CIT0043","first-page":"255","article-title":"Osteoporosis and sarcopenia increase frailty syndrome in the elderly","volume-title":"Front Endocrinol.","author":"Greco","year":"2019"},{"key":"2024040309525123700_CIT0044","first-page":"21","article-title":"Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease","volume-title":"Biofactors.","author":"Cui","year":"2023"},{"key":"2024040309525123700_CIT0045","first-page":"V12170926","article-title":"Monitoring anti-osteoporotic therapy: Bone mineral density or markers of bone turnover","volume":"180","author":"Pedersen","year":"2018","journal-title":"Ugeskr Laeger."},{"key":"2024040309525123700_CIT0046","first-page":"C324","article-title":"The life and times of cellular senescence in skeletal muscle: Friend or foe for homeostasis and adaptation","volume-title":"Am J Physiol Cell Physiol.","author":"Dungan","year":"2023"},{"key":"2024040309525123700_CIT0047","first-page":"41","article-title":"Cellular senescence in musculoskeletal homeostasis, diseases, and regeneration","volume-title":"Bone Res.","author":"Wan","year":"2021"},{"key":"2024040309525123700_CIT0048","first-page":"1246","article-title":"Senolytics improve physical function and increase lifespan in old age","volume-title":"Nat Med.","author":"Xu","year":"2018"},{"key":"2024040309525123700_CIT0049","first-page":"e13528","article-title":"Deletion of SA beta-Gal+ cells using senolytics improves muscle regeneration in old mice","volume-title":"Aging 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