Identification and evaluation of citrus peel-derived polymethoxyflavonoids as natural SIRT1 activators

• A non-fluorometric MS-based assay enables reliable SIRT1 evaluation. • Citrus peel extracts contain compounds that promote SIRT1 activity. • PMFs are identified as key activators of SIRT1 deacetylase activity. • Heptamethoxyflavone (HMF) shows the strongest SIRT1 activation among tested PMFs. • Citrus peels are a rich source of food-derived SIRT1 activators.