Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence.

ABSTRACT: Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy-prone mouse models uncovered an unanticipated link between CIN and aging. Using young to old-aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age-associated CIN. We found that elderly cells have an increased number of stable kinetochore-microtubule (k-MT) attachments and decreased efficiency in the correction of imprope

SUBMITTER: Barroso-Vilares M 

PROVIDER: S-EPMC7202060 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature