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Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis, thereby promoting chronic systemic inflammation, tissue fibrosis, stem-cell dysfunction and propagation of secondary senescence. Experimental genetic and pharmacological evidence supports a contributory and in several contexts causal role for senescent cells in cardiovascular, metabolic, musculoskeletal, fibrotic and neurodegenerative disorders. These findings have accelerated the development of senotherapeutic strategies, including senolytics, senomorphics and immune-mediated clearance approaches, with early clinical studies showing preliminary evidence of functional benefit in idiopathic pulmonary fibrosis and diabetic kidney disease. However, clinical translation remains constrained by senescence heterogeneity, limited biomarker specificity and unresolved long-term safety concerns. Improved molecular, spatial and functional resolution of senescent states will be essential for developing biomarker-guided and tissue-specific interventions that preserve the beneficial functions of transient senescence while limiting its chronic deleterious effects.<\/jats:p>","DOI":"10.1007\/s10522-026-10477-2","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:33:56Z","timestamp":1784777636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cellular senescence and inflammageing: from mechanisms to senotherapeutic interventions"],"prefix":"10.1007","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6995-123X","authenticated-orcid":false,"given":"Piotr Pawe\u0142","family":"Chmielewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"10477_CR1","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ncb2784","volume":"15","author":"JC Acosta","year":"2013","unstructured":"Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. 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