Chromosomal instability and pro-inflammatory response in aging.

ABSTRACT

Aging refers to the progressive deterioration of tissue and organ function over time. Increasing evidence points to the accumulation of highly damaged cell cycle-arrested cells with age (cellular senescence) as major reason for the development of certain aging-associated diseases. Recent studies have independently shown that aneuploidy, an abnormal chromosome set, occurs in senescent cells, and that the accumulation of cytoplasmic DNA driven by faulty chromosome segregation during mitosis aids in the establishment of senescence and its associated secretory phenotype known as SASP. Here we review the emerging link between chromosomal instability (CIN) and senescence in the context of aging, with emphasis on the cGAS-STING pathway activation and its role in the development of the SASP. Based on current evidence, we propose that age-associated CIN in mitotically active cells contributes to aging and its associated diseases, and we discuss the inhibition of CIN as a potential strategy to prevent the generation of aneuploid senescent cells and thereby to delay aging.