{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:46:37Z","timestamp":1787323597046,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hutchinson\u2010Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by the early development of pathological features associated with aging, ultimately leading to premature death. HGPS primarily affects tissues of mesenchymal origin, as evidenced by the clinical manifestations characteristic of this premature aging disorder, including, but not limited to, osteoporosis, muscle wasting, lipodystrophy, and cardiovascular disease. In this study, we used preclinical mouse models and both genetic and translational approaches to investigate whether an antiresorptive strategy, based on RANKL targeting, ameliorated the bone loss phenotype of progeroid mice. Here we show that osteocyte\u2010derived RANKL deletion in the\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mouse model of HGPS reverted bone loss in both long bones and vertebrae. These mice also exhibited increased grip strength and improved endurance capacity. Furthermore,\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice showed increased survival upon osteocyte\u2010specific RANKL deletion. Notably, the use of a translational approach based on the administration of a neutralizing antibody against RANKL also restored bone mass, reduced muscle fibrosis, and extended the lifespan of\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Altogether, these findings support that targeting RANKL exerts a beneficial effect on both osseous and extra\u2010osseous phenotypes of HGPS, suggesting the potential of this therapeutic approach to explore in the treatment of this disease.\n                  <\/jats:p>","DOI":"10.1111\/acel.70655","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:01:41Z","timestamp":1786338101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting\n                    <scp>RANKL<\/scp>\n                    Prevents Bone Loss, Improves Muscle Function and Extends Lifespan in Progeroid Mice"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5733-9839","authenticated-orcid":false,"given":"Sandra","family":"Freitas\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA) Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1962-9728","authenticated-orcid":false,"given":"Alejandra","family":"Valle\u2010Cao","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA) Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3262-9764","authenticated-orcid":false,"given":"Francisco","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Transg\u00e9nicos, Servicios Cient\u00edfico\u2010T\u00e9cnicos. Bioterio Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Fern\u00e1ndez\u2010Sanjurjo","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Funcional, \u00c1rea de Fisiolog\u00eda, Facultad de Medicina Universidad de Oviedo  Oviedo Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-680X","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Fern\u00e1ndez\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Morfolog\u00eda y Biolog\u00eda Celular, Facultad de Medicina Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Loredo","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, \u00c1rea de Pediatr\u00eda, Facultad de Medicina Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Fern\u00e1ndez\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Histopatolog\u00eda Molecular, IUOPA Universidad de Oviedo  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-7007","authenticated-orcid":false,"given":"Carmen","family":"Fiuza\u2010Luces","sequence":"additional","affiliation":[{"name":"Physical Activity and Health Research Group Research Institute of the Hospital 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Lucia","sequence":"additional","affiliation":[{"name":"Department of Sport Sciences, Faculty of Medicine, Health and Sports Universidad Europea de Madrid  Madrid Spain"},{"name":"CIBER of Frailty and Healthy Aging Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez\u2010Ot\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA) Universidad de Oviedo  Oviedo Spain"},{"name":"Facultad de Ciencias de la Vida y la Naturaleza Universidad Nebrija  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6360-5205","authenticated-orcid":false,"given":"Alejandro","family":"L\u00f3pez\u2010Soto","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA) Universidad de Oviedo  Oviedo Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)  Oviedo 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