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Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key \u201chub\u201d proteins involved in their activation.<\/jats:p>\n                  <jats:p>\n                    RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR included\n                    <jats:italic>Gc<\/jats:italic>\n                    ,\n                    <jats:italic>Plg<\/jats:italic>\n                    ,\n                    <jats:italic>Irf7<\/jats:italic>\n                    ,\n                    <jats:italic>Ifit3<\/jats:italic>\n                    ,\n                    <jats:italic>Usp18<\/jats:italic>\n                    ,\n                    <jats:italic>Rsad2<\/jats:italic>\n                    ,\n                    <jats:italic>Blm<\/jats:italic>\n                    and\n                    <jats:italic>RT1-A2<\/jats:italic>\n                    , whilst those exclusively implicated in CR responses included\n                    <jats:italic>Alb<\/jats:italic>\n                    ,\n                    <jats:italic>Apoa1<\/jats:italic>\n                    ,\n                    <jats:italic>Ambp<\/jats:italic>\n                    ,\n                    <jats:italic>F2<\/jats:italic>\n                    ,\n                    <jats:italic>Apoh<\/jats:italic>\n                    ,\n                    <jats:italic>Orm1<\/jats:italic>\n                    ,\n                    <jats:italic>Mx1<\/jats:italic>\n                    ,\n                    <jats:italic>Oasl2<\/jats:italic>\n                    and\n                    <jats:italic>Rtp4<\/jats:italic>\n                    . Hub genes involved in ageing but unaffected by CR included\n                    <jats:italic>Fgg<\/jats:italic>\n                    ,\n                    <jats:italic>Fga<\/jats:italic>\n                    ,\n                    <jats:italic>Fgb<\/jats:italic>\n                    and\n                    <jats:italic>Serpinc1<\/jats:italic>\n                    . In conclusion, this comprehensive RNA sequencing study highlights gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia.\n                  <\/jats:p>","DOI":"10.1186\/s12864-024-11051-1","type":"journal-article","created":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T21:38:10Z","timestamp":1736717890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing"],"prefix":"10.1186","volume":"26","author":[{"given":"Gulam","family":"Altab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Merry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles W.","family":"Beckett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Raina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Goljanek-Whysall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"de Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"11051_CR1","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1111\/jgs.16517","volume":"68","author":"PM Cawthon","year":"2020","unstructured":"Cawthon PM, et al. 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