{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:17Z","timestamp":1788412517479,"version":"build-2803163510"},"reference-count":104,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/13917\u20106"],"award-info":[{"award-number":["2021\/13917\u20106"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Ageing leads to changes in body composition, including increased adiposity and reduced skeletal muscle mass and force. The alterations in ageing skeletal muscle result from impaired proteostasis driven by factors such as chronic inflammation, hormonal changes and reduced nutrient absorption. Those age\u2010related changes in body composition and skeletal muscle compromise mobility and increase the risk of falls, fractures and metabolic disorders. Tauroursodeoxycholic acid (TUDCA), a bile acid with known benefits in chronic diseases, has been shown by our group to improve cognition and metabolic homeostasis in ageing and Alzheimer's disease mouse models. Interestingly, in previous studies, TUDCA treatment was also associated with increased skeletal muscle mass in ageing mice, leading us to hypothesize that TUDCA could target skeletal muscle to reduce age\u2010related muscle loss. To explore this, we treated 18\u2010month\u2010old C57BL\/6 mice with TUDCA or vehicle for 20\u00a0days, using 3\u2010month\u2010old mice as a young control group. We demonstrate that TUDCA treatment decreases body weight while increasing skeletal muscle mass, restores muscle fibre size and preserves functional integrity. Additionally, TUDCA enhances skeletal muscle insulin sensitivity through increased AKT activation and reduces tissue inflammation. Such improvements collectively support the restoration of skeletal muscle proteostasis, as indicated by increased protein synthesis and phosphorylation of key anabolic signalling pathways, including ribosomal protein S6 kinase beta\u20101 (P70S6K) and eukaryotic translation initiation factor 4E\u2010binding protein 1 (4EBP1). These findings contribute to a better understanding of TUDCA's actions on skeletal muscles of ageing mice and highlight its role as a promising strategy against age\u2010related muscle loss.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70592-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Tauroursodeoxycholic acid (TUDCA) treatment attenuates skeletal muscle loss in ageing mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TUDCA improves skeletal muscle insulin sensitivity and restores AKT signalling.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TUDCA exerts an anti\u2010inflammatory effect in skeletal muscle of ageing mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TUDCA emerges as a potential therapy for age\u2010related skeletal muscle loss.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290683","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:01:26Z","timestamp":1778864486000},"page":"4795-4814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tauroursodeoxycholic acid (TUDCA) ameliorates age\u2010related skeletal muscle loss"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1959-8634","authenticated-orcid":false,"given":"Marina S.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Obesity and Comorbidities Research Center, Department of Structural and Functional Biology University of Campinas, UNICAMP  Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Barssotti","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology, Department of Structural and Functional Biology University of Campinas, UNICAMP  Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-9793","authenticated-orcid":false,"given":"Lohanna M. B. Dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Obesity and Comorbidities Research Center, Department of Structural and Functional Biology University of Campinas, UNICAMP  Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas R. 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