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

2018-07-19Journal article Restricted access
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dc.contributor.authorMacedo, Joana Catarina
dc.contributor.authorVaz, Sara
dc.contributor.authorBakker, Bjorn
dc.contributor.authorRibeiro, Rui
dc.contributor.authorBakker, Petra Lammigje
dc.contributor.authorEscandell, Jose Miguel
dc.contributor.authorFerreira, Miguel Godinho
dc.contributor.authorMedema, René
dc.contributor.authorFoijer, Floris
dc.contributor.authorLogarinho, Elsa
dc.date.accessioned2018-09-04T11:17:56Z
dc.date.available2018-09-04T11:17:56Z
dc.date.issued2018-07-19
dc.descriptionThis 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/s41467-018-05258-6pt_PT
dc.descriptionThis 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#Sec36pt_PT
dc.description.abstractAneuploidy, 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.pt_PT
dc.description.sponsorshipE.L. holds an FCT Investigator Postdoctoral Grant (IF/00916/2014) from FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior). FCT Fellowships (SFRH/BD/74002/2010; SFRH/BD/125017/2016; PD/BD/128000/2016) supported J.C.M., S.V., and R.R. The following project grants supported this work: National Funds through FCT under the project PTDC/BEX-BCM/ 2090/2014 ; NORTE-01-0145-FEDER-000029 funded by North Regional Operational Program (NORTE2020) under PORTUGAL 2020 Partnership Agreement through Regional Development Fund (FEDER); NORTE-07-0124-FEDER-000003 co-funded by North Regional Operational Program (ON.2) through FEDER and by FCT; and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/PORTUGAL 2020 through FEDER and by FCT; Foundation Pediatric Oncology Groningen grant and Dutch Cancer Society grant 2012-RUG-5549 to F.F.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMacedo, 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.pt_PT
dc.identifier.doi10.1038/s41467-018-05258-6pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/888
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relationIF/00916/2014pt_PT
dc.relationAge-dependent sensitivity to anti-mitotics: the role of FoxM1 and its therapeutic potential
dc.relationIn vivo amelioration of aging hallmarks by transcriptional modulaton of mitotic proficiency
dc.relationNORTE-01-0145-FEDER-000029pt_PT
dc.relationNORTE-07-0124-FEDER-000003pt_PT
dc.relationPOCI- 01-0145-FEDER-007274pt_PT
dc.relationCOMPETE 2020/PORTUGAL 2020pt_PT
dc.relation2012-RUG-5549pt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-018-05258-6pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAneuploidypt_PT
dc.subjectChromosome segregationpt_PT
dc.subjectMechanisms of diseasept_PT
dc.subjectSenescencept_PT
dc.titleFoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescencept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAge-dependent sensitivity to anti-mitotics: the role of FoxM1 and its therapeutic potential
oaire.awardTitleIn vivo amelioration of aging hallmarks by transcriptional modulaton of mitotic proficiency
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F74002%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F125017%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/PD%2FBD%2F128000%2F2016/PT
oaire.citation.endPage17pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume9pt_PT
oaire.fundingStreamSFRH
oaire.fundingStreamPOR_NORTE
oaire.fundingStreamPOR_NORTE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationd9217174-fa32-40f1-827d-1c60198043bc
relation.isProjectOfPublicatione1f94e45-a3b1-4861-9db6-1383930e3094
relation.isProjectOfPublicationf5fca5c7-5d9b-4e96-a527-9dfbb52f7650
relation.isProjectOfPublication.latestForDiscoveryd9217174-fa32-40f1-827d-1c60198043bc

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