Targeted clearance of p21- but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity.

ABSTRACT: Cellular senescence, which is a major cause of tissue dysfunction with aging and multiple other conditions, is known to be triggered by p16^Ink4a or p21^Cip1 , but the relative contributions of each pathway toward inducing senescence are unclear. Here, we directly addressed this issue by first developing and validating a p21-ATTAC mouse with the p21^Cip1 promoter driving a "suicide" transgene encoding an inducible caspase-8 which, upon induction, selectively kills p21^Cip1 -expressing senescent cells. Next, we used the p21-ATTAC mouse and the established p16-INK-ATTAC mouse to directly compare the contributions of p21^Cip1 versus p16^Ink4a in driving cellular senescence in a condition where a tissue phenotype (bone loss and increa

SUBMITTER: Chandra A 

PROVIDER: S-EPMC9124310 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature