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Here we show, through direct live-cell imaging of young, middle-aged, and old-aged primary human dermal fibroblasts, that aneuploidy increases with aging due to general dysfunction of the mitotic machinery. Increased chromosome mis-segregation in elderly mitotic cells correlates with an early senescence-associated secretory phenotype (SASP) and repression of Forkhead box M1 (FoxM1), the transcription factor that drives G2\/M gene expression. FoxM1 induction in elderly and Hutchison\u2013Gilford progeria syndrome fibroblasts prevents aneuploidy and, importantly, ameliorates cellular aging phenotypes. Moreover, we show that senescent fibroblasts isolated from elderly donors\u2019 cultures are often aneuploid, and that aneuploidy is a key trigger into full senescence phenotypes. Based on this feedback loop between cellular aging and aneuploidy, we propose modulation of mitotic efficiency through FoxM1 as a potential strategy against aging and progeria syndromes.<\/jats:p>","DOI":"10.1038\/s41467-018-05258-6","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T11:02:13Z","timestamp":1531479733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence"],"prefix":"10.1038","volume":"9","author":[{"given":"Joana Catarina","family":"Macedo","sequence":"first","affiliation":[]},{"given":"Sara","family":"Vaz","sequence":"additional","affiliation":[]},{"given":"Bjorn","family":"Bakker","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3759-2399","authenticated-orcid":false,"given":"Rui","family":"Ribeiro","sequence":"additional","affiliation":[]},{"given":"Petra Lammigje","family":"Bakker","sequence":"additional","affiliation":[]},{"given":"Jose Miguel","family":"Escandell","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-7183","authenticated-orcid":false,"given":"Miguel Godinho","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Ren\u00e9","family":"Medema","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-3127","authenticated-orcid":false,"given":"Floris","family":"Foijer","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-0744","authenticated-orcid":false,"given":"Elsa","family":"Logarinho","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,7,19]]},"reference":[{"key":"5258_CR1","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/212823a0","volume":"212","author":"PA Jacobs","year":"1966","unstructured":"Jacobs, P. 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