Late Life Supplementation of 25-Hydroxycholesterol Reduces Aortic Stiffness and Cellular Senescence in Mice.

ABSTRACT: Stiffening of the aorta is a key antecedent to cardiovascular diseases (CVD) with aging. Age-related aortic stiffening is driven, in part, by cellular senescence-a hallmark of aging defined primarily by irreversible cell cycle arrest. In this study, we assessed the efficacy of 25-hydroxycholesterol (25HC), an endogenous cholesterol metabolite, as a naturally occurring senolytic to reverse vascular cell senescence and reduce aortic stiffness in old mice. Old (22-26 months) p16-3MR mice, a transgenic model allowing for genetic clearance of p16-positive senescent cells with ganciclovir (GCV), were administered vehicle, 25HC, or GCV to compare the efficacy of the experimental 25HC senolytic versus genetic clearance of senescent cells. We found that short-term (5d) treatment with 25HC reduced a

SUBMITTER: Mahoney SA 

PROVIDER: S-EPMC12341771 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature