25-Hydroxycholesterol as a Basis for Senolytic Therapy

25-hydroxycholesterol is an oxidized form of cholesterol, and researchers here demonstrate that it is senolytic to some degree in mice. This may be competitive with existing first generation senolytics; from the paper, it looks like it clears about half of the excess of senescent cells present in old mice, in muscle tissue at least. Like all other senolytics, its effectiveness likely varies widely by tissue type and location in the body. Oxidized cholesterols are largely thought to be harmful in the body, particularly because they can cause macrophages to become dysfunctional and accelerate the progression of atherosclerosis. It is unclear as to whether that could prove to be a blocking issue at the sort of doses and schedules used in senolytic therapy.

Researchers have shown that the endogenous metabolite 25-hydroxycholesterol (25HC) significantly reduced the burden of senescent cells in multiple cell types in both mice and human cell culture, and in live mice, where it showed particular efficacy in skeletal muscle. "Given that 25HC shares no common molecular motifs with other senolytics, it appears that this molecule represents a brand new class of potential interventions."

25HC is a little understood oxidized lipid involved in cholesterol metabolism. The team identified it after discovering that the molecule disrupted cellular senescence in CRYAB, a small heat shock protein which was upregulated upon senescence in nine different cell types from two species,...

Source: Fight Aging! - February 9, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs