Sirtuins – Histone Deacetylases Influencing Gene Transcription

Abstract

Sirtuins rank among class III histone deacetylases which deacetylate N^ε-acetyllysine residues in an unusual chemical reaction that consumes NAD⁺ and releases nicotinamide, the deacetylated substrate and a novel product, 2'-O-acetyladenosine diphosphoribose. Sirtuins influence a wide range of biological functions and are required for gene silencing. They are also responsible for lifespan extension by calorie restriction. Their mechanism of action, means of modulating their activity and enzymatic targets, with the focus on age-related diseases, are discussed.