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Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM\/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM\/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis of the nucleus pulposus tissue. Transcriptomic analysis revealed tissue-specific effects of the treatment, with cell cycle regulation and JNK signaling being commonly affected across different tissue types. A comparison of SM\/J data with DQ-mediated aging-dependent amelioration of disc degeneration in C57BL\/6\u2009N mice identified\n                    <jats:italic>Junb<\/jats:italic>\n                    and\n                    <jats:italic>Zfp36l1<\/jats:italic>\n                    signaling as shared DQ targets in the mouse disc. Notably, the in vitro inhibition studies of the JUN pathway in human degenerated NP cells mimicked the benefits of DQ, namely, a reduction in senescence and SASP. This study reinforces the efficacy of senolytic treatment in ameliorating local senescence and intervertebral disc fibrosis.\n                  <\/jats:p>","DOI":"10.1038\/s41413-026-00526-4","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:59:52Z","timestamp":1776131992000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM\/J mice"],"prefix":"10.1038","volume":"14","author":[{"given":"Emanuel J.","family":"Novais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia K.","family":"Ottone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjana","family":"Jagannath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Jesutofunmi","family":"Akande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-9761","authenticated-orcid":false,"given":"Ruteja A.","family":"Barve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makarand V.","family":"Risbud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"526_CR1","doi-asserted-by":"publisher","first-page":"P1789","DOI":"10.1016\/S0140-6736(18)32279-7","volume":"392","author":"Collaborators GBD 2017 Disease and Injury Incidence and Prevalence.","year":"2018","unstructured":"Collaborators GBD 2017 Disease and Injury Incidence and Prevalence. 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