Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/888
Título: FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Autor: Macedo, Joana Catarina
Vaz, Sara
Bakker, Bjorn
Ribeiro, Rui
Bakker, Petra Lammigje
Escandell, Jose Miguel
Ferreira, Miguel Godinho
Medema, René
Foijer, Floris
Logarinho, Elsa
Palavras-chave: Aneuploidy
Chromosome segregation
Mechanisms of disease
Senescence
Data: 19-Jul-2018
Editora: Nature Publishing Group
Citação: Macedo, J.C., Vaz, S., Bakker, B., Ribeiro, R., Bakker, P.L., Escandell, J.M., Ferreira, M.G., Medema, R., Foijer, F., Logarinho, E. (2018). FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nat Commun. 9(1):2834.
Resumo: Aneuploidy, an abnormal chromosome number, has been linked to aging and age-associated diseases, but the underlying molecular mechanisms remain unknown. 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-Gilford progeria syndrome fibroblasts prevents aneuploidy and, importantly, ameliorates cellular aging phenotypes. Moreover, we show that senescent fibroblasts isolated from elderly donors' 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.
Descrição: This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.nature.com/articles/s41467-018-05258-6
This deposit is composed by the main article and the supplementary materials are present in the publisher's page in the following link: https://www.nature.com/articles/s41467-018-05258-6#Sec36
Peer review: yes
URI: http://hdl.handle.net/10400.7/888
DOI: 10.1038/s41467-018-05258-6
Versão do Editor: https://www.nature.com/articles/s41467-018-05258-6
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