Publication

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

Macedo, J. C., Vaz, S., Bakker, B., Ribeiro, R., Bakker, P. L., Escandell, J. M., Ferreira, M. G., Medema, R., Foijer, F. & Logarinho, E., 19-Jul-2018, In : Nature Communications. 9, 1, 17 p., 2834.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Macedo, J. C., Vaz, S., Bakker, B., Ribeiro, R., Bakker, P. L., Escandell, J. M., ... Logarinho, E. (2018). FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nature Communications, 9(1), [2834]. https://doi.org/10.1038/s41467-018-05258-6

Author

Macedo, Joana Catarina ; Vaz, Sara ; Bakker, Bjorn ; Ribeiro, Rui ; Bakker, Petra Lammigje ; Escandell, Jose Miguel ; Ferreira, Miguel Godinho ; Medema, René ; Foijer, Floris ; Logarinho, Elsa. / FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. In: Nature Communications. 2018 ; Vol. 9, No. 1.

Harvard

Macedo, JC, Vaz, S, Bakker, B, Ribeiro, R, Bakker, PL, Escandell, JM, Ferreira, MG, Medema, R, Foijer, F & Logarinho, E 2018, 'FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence', Nature Communications, vol. 9, no. 1, 2834. https://doi.org/10.1038/s41467-018-05258-6

Standard

FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. / Macedo, Joana Catarina; Vaz, Sara; Bakker, Bjorn; Ribeiro, Rui; Bakker, Petra Lammigje; Escandell, Jose Miguel; Ferreira, Miguel Godinho; Medema, René; Foijer, Floris; Logarinho, Elsa.

In: Nature Communications, Vol. 9, No. 1, 2834, 19.07.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Macedo JC, Vaz S, Bakker B, Ribeiro R, Bakker PL, Escandell JM et al. FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence. Nature Communications. 2018 Jul 19;9(1). 2834. https://doi.org/10.1038/s41467-018-05258-6


BibTeX

@article{01f8fe5e90174c049a91f77560fe7991,
title = "FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence",
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.",
author = "Macedo, {Joana Catarina} and Sara Vaz and Bjorn Bakker and Rui Ribeiro and Bakker, {Petra Lammigje} and Escandell, {Jose Miguel} and Ferreira, {Miguel Godinho} and Ren{\'e} Medema and Floris Foijer and Elsa Logarinho",
year = "2018",
month = "7",
day = "19",
doi = "10.1038/s41467-018-05258-6",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence

AU - Macedo, Joana Catarina

AU - Vaz, Sara

AU - Bakker, Bjorn

AU - Ribeiro, Rui

AU - Bakker, Petra Lammigje

AU - Escandell, Jose Miguel

AU - Ferreira, Miguel Godinho

AU - Medema, René

AU - Foijer, Floris

AU - Logarinho, Elsa

PY - 2018/7/19

Y1 - 2018/7/19

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-05258-6

DO - 10.1038/s41467-018-05258-6

M3 - Article

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2834

ER -

ID: 63205559