{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T23:44:23Z","timestamp":1786319063506,"version":"build-2736575974"},"posted":{"date-parts":[[2026,3,3]]},"group-title":"Cancer Biology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["AG082681"],"award-info":[{"award-number":["AG082681"]}]},{"name":"NIH","award":["AG062413"],"award-info":[{"award-number":["AG062413"]}]},{"name":"NIH","award":["AG086085"],"award-info":[{"award-number":["AG086085"]}]},{"name":"NIH","award":["AG076515"],"award-info":[{"award-number":["AG076515"]}]},{"name":"NIH","award":["K12 CA90628-23"],"award-info":[{"award-number":["K12 CA90628-23"]}]},{"name":"NIH","award":["AG R01055529"],"award-info":[{"award-number":["AG R01055529"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cellular senescence has been implicated in the pathophysiology of radiotherapy-related bone loss. Based on our previous work, clearance of senescent cells using genetic and pharmacological tools alleviates the anomalies associated with radiation-associated bone deterioration. The pro-inflammatory senescence associated secretome referred to as senescence associated secretory phenotype (SASP), is a hallmark of cellular senescence. The modulation of SASP by senomorphic drugs, potentially can suppress the pro-inflammatory secretome of senescent cells, irrespective of the underlying senescence mechanism. In this study we tested a senomorphic drug, ruxolitinib, a Janus kinase inhibitor (JAKi), during acute and chronic radiotherapy related effects on the bone. Our clinical data indicate an early increase in several pro-inflammatory SASP proteins following radiotherapy of spinal metastasis in prostate cancer patients. Longitudinal assessment of SASP-related genes confirmed this acute elevation in several SASP markers in systemic circulation following irradiation of mouse femurs. In a proof-of-concept study, following two preclinical radiotherapy regimens of cumulative doses of 30Gy (5 x 6Gy) and 60Gy (5 x 12Gy), a senomorphic approach of JAKi treatment was more effective in alleviating radiation-related bone loss compared to the senolytic cocktail of D+Q. Early and intermittent suppression of SASP using JAK inhibitors alleviated chronic bone deterioration, diminished telomere dysfunction, lowered senescence and SASP marker expression, reduced bone-marrow adiposity, and mitigated radiation related lymphatic impairment. Overall, our study shows that early targeting of SASP proteins could be a potential therapeutic to prevent radiotherapy-related chronic bone loss and risk of fractures.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Radiotherapy as part of cancer treatment is correlated with an acute increase in senescent cells. Here we show that the pro-inflammatory senescence associated secretory phenotype (SASP) becomes much more prominent soon after radiotherapy in both patients and mice. Suppression of the SASP using a Janus kinase inhibitor, ruxolitinib, reduced the overall senescent cell burden, improved bone architecture by promoting bone formation, reduced bone marrow adiposity, and mitigated radiation-induced lymphatic impairment. Overall, these findings suggest that early inhibition of the SASP may help mitigate several bone anomalies and prevent long-term bone loss and fractures after radiotherapy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"708630v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.01.708630","type":"posted-content","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T20:20:16Z","timestamp":1772569216000},"source":"Crossref","is-referenced-by-count":1,"title":["Suppression of early pro-inflammatory senescent signature post-radiotherapy mitigates chronic bone damage"],"prefix":"10.64898","author":[{"given":"David","family":"Achudhan","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":false,"given":"Jacob","family":"Orme","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqsa","family":"Komel","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khubaib Gul","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"White","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-0418","authenticated-orcid":false,"given":"Nathan K.","family":"LeBrasseur","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4372","authenticated-orcid":false,"given":"Sundeep","family":"Khosla","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Endocrinology, Mayo Clinic, Rochester, MN, 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean S.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"},{"name":"Mayo Clinic Comprehensive Cancer Center, Rochester, MN, 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-9438","authenticated-orcid":false,"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-9669","authenticated-orcid":false,"given":"Abhishek","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026030615050453000_2026.03.01.708630v1.1","doi-asserted-by":"crossref","unstructured":"Dinh, P.A. , et al., Genetic links between multimorbidity and human aging. 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