Whole chromosome instability induces senescence and promotes SASP

Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna

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44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number35218
JournalScientific reports
Volume6
DOIs
StatePublished - Oct 12 2016

ASJC Scopus subject areas

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    Andriani, G. A., Almeida, V. P., Faggioli, F., Mauro, M., Li Tsai, W., Santambrogio, L., Maslov, A., Gadina, M., Campisi, J., Vijg, J., & Montagna, C. (2016). Whole chromosome instability induces senescence and promotes SASP. Scientific reports, 6, [35218]. https://doi.org/10.1038/srep35218