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Increased chromosome segregation defects in elderly mitotic cells correlated with an early senescence-associated secretory phenotype (SASP) and repression of Forkhead box M1 (FoxM1), the transcription factor that drives expression of most G2\/M genes. By restoring FoxM1 levels in elderly and Hutchison-Gilford Progeria Syndrome fibroblasts we prevented aneuploidy and, importantly, ameliorated cellular phenotypes associated with aging. Moreover, senescent fibroblasts isolated from elderly donors\u2019 cultures were mostly aneuploid, suggesting that aneuploidy is a key player in the progression 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":"10.1101\/261008","type":"posted-content","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T04:57:03Z","timestamp":1518065823000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular basis of mitotic decline during human aging"],"prefix":"10.64898","author":[{"given":"Joana Catarina","family":"Macedo","sequence":"first","affiliation":[]},{"given":"Sara","family":"Vaz","sequence":"additional","affiliation":[]},{"given":"Bjorn","family":"Bakker","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Ribeiro","sequence":"additional","affiliation":[]},{"given":"Petra","family":"Bakker","sequence":"additional","affiliation":[]},{"given":"Jose Miguel","family":"Escandell","sequence":"additional","affiliation":[]},{"given":"Miguel Godinho","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Ren\u00e9","family":"Medema","sequence":"additional","affiliation":[]},{"given":"Floris","family":"Foijer","sequence":"additional","affiliation":[]},{"given":"Elsa","family":"Logarinho","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019071818594019000_261008v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/212823a0"},{"key":"2019071818594019000_261008v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3245"},{"key":"2019071818594019000_261008v1.3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0921-8734(95)00016-Y","article-title":"Sex chromosome aneuploidy and aging","volume":"338","year":"1995","journal-title":"Mutat. 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