{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:53:10Z","timestamp":1791258790270,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:p>Cellular senescence, a key feature of ageing, involves irreversible cell cycle arrest and the secretion of pro\u2010inflammatory senescence\u2010associated secretory phenotype (SASP) factors, which contribute to tissue degeneration and age\u2010related diseases. Targeting senescent cells with senolytics, senomorphics and anti\u2010ageing therapies marks a major shift in translational geroscience, with the potential to delay or reverse age\u2010related conditions. A systematic review and narrative synthesis was conducted in accordance with PRISMA 2020 guidelines. Eligible human clinical studies evaluating pharmacological interventions targeting cellular senescence were included, comprising randomized and nonrandomized clinical trials and pilot studies reporting clinical, functional or senescence\u2010associated outcomes. Data on study characteristics, interventions, efficacy, safety and senescence\u2010associated biomarkers were extracted and synthesized qualitatively. Six completed clinical studies were included in the evidence synthesis, with one additional ongoing clinical trial identified separately. Senolytic interventions, particularly dasatinib plus quercetin, showed preliminary improvements in selected functional outcomes and reductions in senescence\u2010associated biomarkers, while senomorphic and mTOR\u2010targeting interventions demonstrated effects on selected tissue and immune\u2010related outcomes. Reported adverse events were generally mild or manageable, but small sample sizes and short follow\u2010up limited assessment of uncommon and long\u2010term safety risks. Current evidence suggests that pharmacological targeting of cellular senescence is feasible and may produce measurable biological and functional effects in humans, but evidence remains insufficient to establish clinical efficacy or long\u2010term safety. Senolytic and senomorphic strategies should therefore be considered investigational rather than established therapies. Larger, adequately powered randomized trials with standardized senescence biomarkers, clinically meaningful outcomes, longer follow\u2010up and systematic safety assessment are needed.<\/jats:p>","DOI":"10.1002\/bcp.70871","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:23:06Z","timestamp":1791256986000},"source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic reversal of cellular senescence: A systematic review of senolytics, senomorphics and anti\u2010ageing therapies in human clinical trials"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3049-528X","authenticated-orcid":false,"given":"Hitesha","family":"Trivedi","sequence":"first","affiliation":[{"name":"Department of Pharmacology Zydus Medical College and Hospital  Dahod India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Zydus Medical 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