{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:04:48Z","timestamp":1793397888559,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1009921"],"award-info":[{"award-number":["2020R1C1C1009921"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro\u2010regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53\/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint. Mass spectrometry coupled with protein interaction network analysis and biophysical stability prediction of extracted joint proteins revealed divergent responses to senolysis between young and aged animals, broadly suggesting that knee regeneration and cellular stress programs are contrarily poised to respond as a function of age. These opposing responses include differing signatures of protein\u2010by\u2010protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation\u2010induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics.<\/jats:p>","DOI":"10.1111\/acel.13979","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T05:51:10Z","timestamp":1695707470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Senolytic treatment reduces oxidative protein stress in an aging male murine model of post\u2010traumatic osteoarthritis"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-2577","authenticated-orcid":false,"given":"Alexander F.","family":"Chin","sequence":"first","affiliation":[{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-5140","authenticated-orcid":false,"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina C.","family":"Clement","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Englander Institute for Precision Medicine, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younghwan","family":"Choi","sequence":"additional","affiliation":[{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland 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Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-1996","authenticated-orcid":false,"given":"Jennifer H.","family":"Elisseeff","sequence":"additional","affiliation":[{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Bloomberg\u2010Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine  Baltimore Maryland 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