Intermittent Fisetin Supplementation Improves Vascular Function in Old Mice

Given that the Interventions Testing Program found that fisetin supplementation did not extend life in mice, it is interesting to see that other researchers are still demonstrating that this intervention clears senescent cells and, as a direct consequence, improves function in older mice. Fisetin is something of a puzzle in this respect, and the Mayo Clinic needs to hurry up and publish useful data from their ongoing phase 2 human trials of fisetin supplementation.

Cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to age-related arterial dysfunction, in part, by promoting oxidative stress and inflammation, which reduce the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice. We found that fisetin decreased cellular senescence in human endothelial cell culture.

In old mice, vascular cell senescence and SASP-related inflammation were lower 1 week after the final dose of oral intermittent (1 week on-2 weeks off-1 weeks on dosing) fisetin supplementation. Old fisetin-supplemented mice had higher endothelial function. Leveraging old p16-3MR mice, a transgenic model allowing genetic clearance of p16INK4A-positive senescent cells, we found that ex vivo removal of senescent cells from arteries isolated from controls but not fi...

Source: Fight Aging! - December 18, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs