{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:32:57Z","timestamp":1789770777385,"version":"4.0.1"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2022-NR070844"],"award-info":[{"award-number":["RS-2022-NR070844"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["RS-2022-NR068998"],"award-info":[{"award-number":["RS-2022-NR068998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Senescent cells secrete pro-inflammatory cytokines, collectively referred to as the senescence-associated secretory phenotype (SASP). Certain pro-inflammatory SASP factors are known to inhibit the differentiation of bone-forming osteoblast while promoting the differentiation of bone-resorbing osteoclasts, thereby causing osteoporosis. In this study, we screened cabozantinib, a tyrosine kinase inhibitor used to treat medullary thyroid cancer, for its ability to reduce doxorubicin-induced cellular senescence in both osteoblast and osteoclast progenitors. This non-cytotoxic agent suppressed the secretion of SASP factors (e.g., TNF\u03b1, IL1\u03b1, IL1\u03b2, IL6, and CCL2) from senescent osteoblast and osteoclast progenitors, resulting in enhanced osteoblast differentiation and reduced osteoclast differentiation. Furthermore, intraperitoneal administration of cabozantinib to age-related estrogen-deficient mice subjected to ovariectomy prevented bone loss without apparent side effects, increasing osteoblast numbers and reducing osteoclast numbers along the surface of the trabecular bone. In summary, our findings suggest that anti-aging cabozantinib has potential as a preventive anti-osteoporotic agent by promoting osteogenesis and inhibiting osteoclastogenesis through the repression of SASP.<\/jats:p>","DOI":"10.3390\/ijms26157123","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:54:26Z","timestamp":1753343666000},"page":"7123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cabozantinib, an Anti-Aging Agent, Prevents Bone Loss in Estrogen-Deficient Mice by Suppressing Senescence-Associated Secretory Phenotype Factors"],"prefix":"10.3390","volume":"26","author":[{"given":"Jueun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-7805","authenticated-orcid":false,"given":"Jiin","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ryong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Senotherapy-Based Metabolic Disease Control Research Center, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunil","family":"Ha","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7503-9725","authenticated-orcid":false,"given":"Taesoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daewon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"943321","DOI":"10.3389\/fimmu.2022.943321","article-title":"Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism","volume":"13","author":"Cui","year":"2022","journal-title":"Front. 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