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Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy\u2010prone mouse models uncovered an unanticipated link between\n                    <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>\n                    and aging. Using young to old\u2010aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age\u2010associated\n                    <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>\n                    . We found that elderly cells have an increased number of stable kinetochore\u2013microtubule (k\u2010\n                    <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\n                    ) attachments and decreased efficiency in the correction of improper k\u2010\n                    <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\n                    interactions. Chromosome mis\u2010segregation rates in old\u2010aged cells decreased upon both genetic and small\u2010molecule enhancement of\n                    <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>\n                    \u2010depolymerizing kinesin\u201013 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence. Therefore, we provide mechanistic insight into age\u2010associated\n                    <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>\n                    and disclose a strategy for the use of a small\u2010molecule to inhibit age\u2010associated\n                    <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>\n                    and to delay the cellular hallmarks of aging.\n                  <\/jats:p>","DOI":"10.15252\/embr.201949248","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T08:08:40Z","timestamp":1583395720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Small\u2010molecule inhibition of aging\u2010associated chromosomal instability delays cellular senescence"],"prefix":"10.1038","volume":"21","author":[{"given":"Monika","family":"Barroso\u2010Vilares","sequence":"first","affiliation":[{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"Aging and Aneuploidy Group IBMC\u2014Instituto de Biologia Molecular e Celular Universidade do Porto Porto Portugal"},{"name":"Programa doutoral em Biologia Molecular e Celular Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar Universidade do Porto Porto Portugal"}]},{"given":"Joana C","family":"Macedo","sequence":"additional","affiliation":[{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"Aging and Aneuploidy Group IBMC\u2014Instituto de Biologia Molecular e Celular Universidade do Porto Porto Portugal"}]},{"given":"Marta","family":"Reis","sequence":"additional","affiliation":[{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"Aging and Aneuploidy Group IBMC\u2014Instituto de Biologia 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