Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence

This University of Colorado Boulder ageing-research group tested whether taking fisetin intermittently, rather than continuously, could clear out senescent ('zombie') cells from blood vessels in old mice and restore healthier artery function.

Old mice given a pulsed fisetin schedule (a week on, two weeks off, then a week on again) had fewer senescent vascular cells and lower levels of the inflammatory secretions those cells produce, one week after their last dose.

These fisetin-treated old mice also had better endothelial function - the blood vessel lining's ability to relax and dilate via nitric oxide - and stiffer, less flexible arteries were softened by fisetin.

To prove the benefit truly came from clearing senescent cells (rather than a coincidental drug effect), the researchers used a special mouse strain that lets senescent cells be cleared genetically. When they did this in mice already treated with fisetin, there was no further improvement - meaning fisetin's benefit already worked by the same route (senolysis) that direct genetic clearance would achieve.

This is one of the more rigorous senolytic-mechanism papers behind fisetin's cardiovascular reputation, but it remains a mouse study; the intermittent human dosing regimens marketed for fisetin senolytic use have not been validated against this specific pulsed schedule in people.