Life Extension in Drosophila by Histone Deacetylase Inhibitors

Abstract

In the last years, epigenetic regulatory mechanisms are increasingly appreciated as central to a diverse array of age-associated processes such as cellular and organismal senescence, genomic instability, and tumorigenesis. Recently, histone deacetylase inhibitors (HDACIs), a novel class of drugs targeting epigenetic pathways, have been proposed as a highly promising type of drugs with anti-aging effects. This chapter presents an overview of the anti-aging and lifeextending effects of HDACIs such as phenilbutyrate, sodium butyrate, trichistatin A and suberoylanilide hydroxamic acid as well as their plausible mechanism(s) of action in Drosophila melanogaster. Data supporting the hypothesis that life span extension induced by HDACIs may be caused by generalized changes in epigenetic regulation of gene expression are discussed. Overall, findings reviewed in this chapter suggest that uncovering which genetic factors and signaling pathways contributing to healthy aging can be influenced by HDACIs in fruit fly may facilitate the development of new strategies for treating and preventing age-related human diseases and health span extension.