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Normal senescent cells show splicing factor dysregulation, which has not yet been investigated in syndromic senescent cells. We sought to investigate the senescence characteristics and splicing factor expression profiles of progeroid dermal fibroblasts. Natural cellular senescence can be reversed by application of the senomorphic drug, trametinib, so we also investigated its ability to reverse senescence characteristics in syndromic cells. We found that progeroid cultures had a higher senescence burden, but did not always have differences in levels of proliferation, DNA damage repair and apoptosis. Splicing factor gene expression appeared dysregulated across the three syndromes. 10\u00a0\u00b5M trametinib reduced senescent cell load and affected other aspects of the senescence phenotype (including splicing factor expression) in HGPS and Cockayne syndromes. Werner syndrome cells did not demonstrate changes in in senescence following treatment. Splicing factor dysregulation in progeroid cells provides further evidence to support this mechanism as a hallmark of cellular ageing and highlights the use of progeroid syndrome cells in the research of ageing and age-related disease. This study suggests that senomorphic drugs such as trametinib could be a useful adjunct to therapy for progeroid diseases.<\/jats:p>","DOI":"10.1007\/s11357-023-00933-z","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T09:02:27Z","timestamp":1695718947000},"page":"1861-1879","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Senescence, regulators of alternative splicing and effects of trametinib treatment in progeroid syndromes"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4069-3959","authenticated-orcid":false,"given":"Laura R.","family":"Bramwell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-8061","authenticated-orcid":false,"given":"Lorna W.","family":"Harries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"issue":"6","key":"933_CR1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.ceb.2012.08.009","volume":"24","author":"JMP Freije","year":"2012","unstructured":"Freije JMP, L\u00f3pez-Ot\u00edn C. 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