FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence

Joana Catarina Macedo, Sara Vaz, Bjorn Bakker, Rui Ribeiro, Petra Lammigje Bakker, Jose Miguel Escandell, Miguel Godinho Ferreira, René Medema, Floris Foijer and Elsa Logarinho ()
Additional contact information
Joana Catarina Macedo: Universidade do Porto
Sara Vaz: Universidade do Porto
Bjorn Bakker: University Medical Center Groningen
Rui Ribeiro: Universidade do Porto
Petra Lammigje Bakker: University Medical Center Groningen
Jose Miguel Escandell: Instituto Gulbenkian de Ciência
Miguel Godinho Ferreira: Instituto Gulbenkian de Ciência
René Medema: The Netherlands Cancer Institute
Floris Foijer: University Medical Center Groningen
Elsa Logarinho: Universidade do Porto

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05258-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05258-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05258-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().