Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/127074
Author(s): Macedo JC
Vaz S
Bakker B
Ribeiro R
Bakker P
Escandell J
Ferreira M
Medema R
Foijer F
Logarinho E
Title: FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Publisher: Nature
Issue Date: 2018
Abstract: 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.
URI: https://hdl.handle.net/10216/127074
Source: Nature Communications, vol.9(1):2834
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: http://creativecommons.org/licenses/by/4.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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