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.