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DOI | 10.1038/s41467-018-03761-4 |
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence | |
Macedo, Joana Catarina1,2; Vaz, Sara1,2; Bakker, Bjorn3; Ribeiro, Rui1,2; Bakker, Petra Lammigje3; Escandell, Jose Miguel4; Ferreira, Miguel Godinho4,5; Medema, Rene6,7; Foijer, Floris3; Logarinho, Elsa1,2,8 | |
2018-07-19 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Portugal; Netherlands; France |
英文摘要 | 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. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000439111800014 |
WOS关键词 | HUMAN-CELLS ; IN-VIVO ; TRANSCRIPTION FACTOR ; CELLULAR SENESCENCE ; GENE-EXPRESSION ; CANCER-CELLS ; AGE ; PROLIFERATION ; ACTIVATION ; YEAST |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203761 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Porto, Inst Biol Mol & Celular, Aging & Aneuploidy Lab, IBMC, P-4200135 Porto, Portugal; 2.Univ Porto, i3S, P-4200135 Porto, Portugal; 3.Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Aging, NL-9713 AV Groningen, Netherlands; 4.Inst Gulbenkian Ciencias, Telomere & Genome Stabil Lab, P-2781901 Oeiras, Portugal; 5.UNS, Telomere Shortening & Canc Lab, Inst Res Canc & Aging IRCAN, UMR7284,U1081, F-06107 Nice, France; 6.Netherlands Canc Inst, Div Cell Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 7.Netherlands Canc Inst, Canc Genom Ctr, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 8.Univ Porto, Fac Med, Dept Expt Biol, Cell Div Unit, P-4200319 Porto, Portugal |
推荐引用方式 GB/T 7714 | Macedo, Joana Catarina,Vaz, Sara,Bakker, Bjorn,et al. FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Macedo, Joana Catarina.,Vaz, Sara.,Bakker, Bjorn.,Ribeiro, Rui.,Bakker, Petra Lammigje.,...&Logarinho, Elsa.(2018).FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence.NATURE COMMUNICATIONS,9. |
MLA | Macedo, Joana Catarina,et al."FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence".NATURE COMMUNICATIONS 9(2018). |
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