25-hydroxycholesteral (25HC) - A naturally-occurring metabolite is a potent senolytic

New research out of the Buck Institute:

There is a potential new class of senolytics that can remove or mitigate the effects of cellular senescence, a stress response which drives many age-related diseases. Publishing in iScience, researchers at the Buck Institute show the endogenous metabolite 25-hydroxycholesteral (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,” said Buck professor Simon Melov, senior scientist on the study. “It’s most likely going to be useful in multiple contexts of senescence in different disease states, as well as in aging. We’re continuing to refine this molecule and its target, in order to understand how it works in the mouse and human cell types.”

It looks like this research was supported by a company planning to commercialize the compound:

Acknowledgments: Support for this project was from Astellas Pharma Inc., and NIH Grants AG061879, AG0511 and AG055822.

Full Research Paper Pre-proof below:


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Interesting. There are several papers that implicate 25HC in neurodegeneration.m, including Alzheimer’s.

Could support the elevated cholesterol theory (25HC readily crosses the BBB) of neurodegeneration. It’s also made locally in the CNS/microglia.