title: Alkylresorcinols activate SIRT1 and delay ageing in Drosophila melanogaster.
abstract: 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 Vmaxof recombinant SIRT1 for NAD+ and peptide substrate, and that ARs decreased acetylated histone in human monocyte cells by stimulating SIRT1-dependent deacetylation of substrates. ARs also extended the lifespan of Drosophila melanogaster, which was shown to be dependent on functional Sir2. Our results demonstrated that ARs are natural catalytic activators for sirtuin.
authors.affiliation: Department of Food and Nutrition, Yamanashi Gakuin Junior College, 2-4-5 Sakaori, Kofu-shi, Yamanashi 400-8575, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Kayashima
authors.affiliation: Health Care Research Center, Nisshin Pharma Inc., 5-3-1, Fujimino, Saitama 356-8511, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katayanagi
authors.affiliation: Health Care Research Center, Nisshin Pharma Inc., 5-3-1, Fujimino, Saitama 356-8511, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Health Care Research Center, Nisshin Pharma Inc., 5-3-1, Fujimino, Saitama 356-8511, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Fukutomi
authors.affiliation: Health Care Research Center, Nisshin Pharma Inc., 5-3-1, Fujimino, Saitama 356-8511, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hiramoto
authors.affiliation: School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1, Katakura, Hachioji Tokyo 192-0982, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Imai
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D012118:Resorcinols / Q000494:pharmacology*; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D012118:Resorcinols; D013267:Stilbenes; D056564:Sirtuin 1; D000077185:Resveratrol