Alkylresorcinols activate SIRT1 and delay ageing in Drosophila melanogaster.

Sirtuins are enzymes that catalyze NAD+ dependent protein deacetylation. The natural polyphenolic compound resveratrol received renewed interest when recent findings implicated resveratrol as a potent SIRT1 activator capable of mimicking the effects of calorie restriction. However, resveratrol directly interacts with fluorophore-containing peptide substrates. It was demonstrated that the SIRT1 activation of resveratrol is affected by the amino acid composition of the substrate. Resveratrol did increase the enzyme activity in cases in which hydrophobic amino acids are at the +1 position to the acetylated lysine in the substrate. Alkylresorcinols (ARs) are compounds that belong to the family of phenolic lipids, and they are found in numerous biological species. Here we show that the natural activators ARs increased the V