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The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis\u2010driven approach. SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. The most deleterious SC are resistant to apoptosis and have up\u2010regulation of anti\u2010apoptotic pathways which defend SC against their own inflammatory senescence\u2010associated secretory phenotype (SASP), allowing them to survive, despite killing neighbouring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue\u2010destructive SASP. Because SC take weeks to reaccumulate, senolytics can be administered intermittently \u2013 a \u2018hit\u2010and\u2010run\u2019 approach. In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment. As anticipated for agents targeting the fundamental ageing mechanisms that are \u2018root cause\u2019 contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age\u2010related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer\u2019s disease, COVID\u201019, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.<\/jats:p>","DOI":"10.1111\/joim.13141","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T01:21:16Z","timestamp":1595208076000},"page":"518-536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1214,"title":["Senolytic drugs: from discovery to translation"],"prefix":"10.1111","volume":"288","author":[{"given":"J. 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