Whole Chromosome Instability induces senescence and promotes SASP
| Autor: | Cristina Montagna, Francesca Faggioli, Jan Vijg, Wanxia Li Tsai, Judith Campisi, Grasiella A. Andriani, Maurizio Mauro, Vinnycius Pereira Almeida, Laura Santambrogio, Massimo Gadina, Alexander Y. Maslov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Senescence Aging Chromosomal Proteins Non-Histone DNA damage Cells BUB1 Apoptosis Cell Cycle Proteins Protein Serine-Threonine Kinases Biology Fluorescence Article Chromosome segregation 03 medical and health sciences 0302 clinical medicine Chromosomal Instability Chromosome instability Genetics 2.1 Biological and endogenous factors Humans Aetiology Mitosis In Situ Hybridization Cells Cultured Cellular Senescence In Situ Hybridization Fluorescence Cell Proliferation Cultured Multidisciplinary Cohesin fungi Non-Histone Protein-Serine-Threonine Kinases Cell biology Other Physical Sciences Chromosomal Proteins Spindle checkpoint Phenotype 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Biochemistry and Cell Biology DNA Damage |
| Zdroj: | Scientific Reports Scientific reports, vol 6, iss 1 Andriani, GA; Almeida, VP; Faggioli, F; Mauro, M; Li Tsai, W; Santambrogio, L; et al.(2016). Whole chromosome instability induces senescence and promotes SASP. Scientific Reports, 6. doi: 10.1038/srep35218. Lawrence Berkeley National Laboratory: Lawrence Berkeley National Laboratory. Retrieved from: http://www.escholarship.org/uc/item/75p4v4dw |
| ISSN: | 2045-2322 |
| Popis: | Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs). W-CIN induced DNA double strand breaks and elevated oxidative stress, but caused low apoptosis. SAFs of W-CIN cells were remarkably similar to those induced by replicative senescence but occurred in only 13 days versus 4 months. Cultures enriched with not-diploid cells acquired a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A. These findings suggest that W-CIN triggers premature senescence, presumably to prevent the propagation of cells with an abnormal DNA content. Cells deviating from diploidy have the ability to communicate with their microenvironment by secretion of an array of signaling factors. Our results suggest that aneuploid cells that accumulate during aging in some mammalian tissues potentially contribute to age-related pathologies and inflammation through SASP secretion. |
| Databáze: | OpenAIRE |
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