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However, the mechanisms regulating senescence in the intervertebral disc (IVD) and other tissues\/diseases remain poorly understood. Recently, ZNF865 (BLST) was identified as a previously uncharacterized zinc finger protein that regulates a wide array of genes related to protein processing, cell senescence, and DNA damage repair. Here, we show that ZNF865 expression decreases with age and pathology in human and mouse IVD samples. Utilizing CRISPR\u2010guided gene modulation, we show that ZNF865 is necessary for healthy cell function and is a critical protein in regulating senescence and DNA damage in IVD cells, with implications for a wide range of tissues and organs. We also demonstrate that downregulation of ZNF865 induces senescence in asymptomatic human nucleus pulposus (NP) cells. Conversely, restoration in degenerative NP cells mitigates senescence, SASP expression, and DNA damage, enhances ECM anabolism, and restores chromatin accessibility and gene expression to a healthy state. In\u00a0vivo, CRISPRi of ZNF865 induces disc degeneration and painful behaviors. Collectively, our findings establish ZNF865 as a novel regulator of genome stability and a potential therapeutic target for mediating senescence\/DNA damage in aging related diseases.<\/jats:p>","DOI":"10.1111\/acel.70754","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:13:01Z","timestamp":1791605581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZNF865 (BLST) a Novel Regulator of DNA Damage and Cell Senescence in Back Pain"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-8645","authenticated-orcid":false,"given":"Christian","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Levis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8950-6086","authenticated-orcid":false,"given":"Jonah","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-1789","authenticated-orcid":false,"given":"Jacob T.","family":"Polaski","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Mizels","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3303-9649","authenticated-orcid":false,"given":"Molly","family":"Czachor","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-6606","authenticated-orcid":false,"given":"Sarah E.","family":"Gullbrand","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Diekman","sequence":"additional","affiliation":[{"name":"Thurston Arthritis Research Center University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Lampe Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-0590","authenticated-orcid":false,"given":"James C.","family":"Iatridis","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gertz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"},{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City Utah USA"},{"name":"Department of Oncological Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robby D.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City Utah USA"},{"name":"Department of Orthopaedic Surgery University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4184\/asj.2015.9.4.645"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.64242"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jneumeth.2015.08.010","article-title":"Practical Mechanical Threshold Estimation in Rodents Using von Frey Hairs\/Semmes\u2010Weinstein Monofilaments: Towards a Rational Method","volume":"255","author":"Bradman M. 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