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Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the human intervertebral disc, we exposed human nucleus pulposus (hNP) cells directly to the DNA damaging agent cisplatin. Cisplatin\u2010treated hNP cells exhibited rapid phosphorylation of ATM and subsequent increased NF\u2010\u03baB activation, aggrecanolysis, decreased total proteoglycan production and increased expression of markers of senescence, including p21, \u03b3H<jats:sub>2<\/jats:sub>AX and SA\u2010\u00df\u2010gal. Treating cisplatin\u2010exposed hNP cells with an ATM\u2010specific inhibitor negated these effects. In addition, genetic reduction of ATM reduced disc cellular senescence and matrix proteoglycan loss in the progeroid <jats:italic>Ercc1<jats:sup>\u2212\/\u2206<\/jats:sup><\/jats:italic> mouse model of accelerated ageing. These findings suggest that activation of ATM signalling under persistent genotoxic stress promotes disc cellular senescence and matrix homeostatic perturbation. Thus, the ATM signalling pathway represents a therapeutic target to delay the progression of age\u2010associated spine pathologies.<\/jats:p>","DOI":"10.1111\/acel.13162","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T02:56:20Z","timestamp":1592794580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Attenuation of ataxia telangiectasia mutated signalling mitigates age\u2010associated intervertebral disc degeneration"],"prefix":"10.1111","volume":"19","author":[{"given":"Yingchao","family":"Han","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Department of Spine Surgery Shanghai East Hospital School of Medicine Tongji University  Shanghai China"},{"name":"Ferguson Laboratory for Orthopedic and Spine Research Department of Orthopedic Surgery University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Ming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Orthopedic and Spine Research Department of Orthopedic Surgery University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxing","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Shanghai East Hospital School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Dong","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Orthopedic and Spine Research 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