Stress-dependent senomorphic-like activity of buckwheat-derived rutin mediated via SIRT1

Abstract

Sirtuin 1 (SIRT1) is a key NAD⁺-dependent deacetylase regulating cellular metabolism, oxidative stress resistance, and longevity. This study investigates the senomorphic-like effects of buckwheat-derived rutin on SIRT1 under basal and toxic stress conditions. Using in vivo experiments in mice (liver and kidney tissues, n=8/group) and in silico molecular docking, we assessed SIRT1 protein levels and rutin interactions. BPA-induced stress decreased SIRT1 expression (p < 0.05), whereas co-treatment with buckwheat extract restored and elevated SIRT1 above control levels, indicating stress-responsive modulation. Docking analysis revealed strong binding of rutin to the SIRT1 catalytic site (up to –10.3 kcal/mol) with multiple hydrogen bonds, supporting direct modulatory potential. These findings suggest that buckwheat bioactives maintain homeostatic SIRT1 under normal conditions while enhancing its activity under stress, providing a potential dietary strategy to mitigate senescence-associated secretory phenotype (SASP)-related damage.