Lifespan extension and elevatedhspgene expression inDrosophilacaused by histone deacetylase inhibitors

Abstract

The heat shock proteins (Hsps) play a positive role in lifespan determination, and histone acetylation has been shown to be involved in transcription of hsp genes in Drosophila. To further determine if hsp22 and hsp70 expression is correlated with lifespan, and if histone acetylation participates in this process, RNA levels for hsp22 and hsp70 were analyzed throughout the lifespan in the long-lived and short-lived iso-female lines. The results showed that hsp22 and hsp70 RNA levels were higher in long-lived line than in short-lived line and that the longlived flies responded more rapidly to heat but were more tolerant to high temperature. Moreover, we investigated the influences of histone acetylation modification on longevity and on hsp gene expression by using histone deacetylase (HDAC) inhibitors TSA and BuA. The results demonstrated that both inhibitors were able to extend the lifespan and promote hsp22 and hsp70 expression. However, the optimal concentrations of these inhibitors, and probably the mechanisms of their actions, vary with the genetic background. In addition, we showed that HDAC inhibitors caused the hyperacetylation of core histone H3, implicating the involvement of chromatin modulation in hsp gene transcription. These data suggested a close correlation among histone acetylation, hsp gene expression and longevity in D. melanogaster.

Food restriction enhances visual cortex plasticity in adulthood

“…Consistently, it has been previously demonstrated that the use of histone deacetylase inhibitors causes a life span extension 43 and an increase in adult brain plasticity [35][36][37] .…”

Valproic acid extends Caenorhabditis elegans lifespan

“…Histone deacetylase activity has been implicated in the control of lifespan, because drugs that inhibit HDAC activity and mutations that reduce HDAC activity can extend the lifespan of Drosophila (Kang et al, 2002;Rogina et al, 2002;Zhao et al, 2005). To address the role of HDAC inhibition in the mechanism of action of VA in C. elegans, we conducted a structure-activity study.…”

“…Four categories of compounds have been reported to extend C. elegans lifespan: a variety of antioxidant compounds (Harrington & Harley, 1988;Adachi & Ishii, 2000;Melov et al ., 2000;Ishii et al ., 2004;Keaney et al ., 2004); complex mixtures derived from plants (Wu et al ., 2002;Wilson et al ., 2006); resveratrol, a potential modulator of Sir2 activity (Wood et al ., 2004;Bass et al ., 2007); and medications such as heterocyclic anticonvulsant medications that are likely to act by affecting neural activity (Evason et al ., 2005;Petrascheck et al ., 2007;McColl et al ., 2008). Drosophila melanogaster has also been an important system for the discovery of drugs that extend lifespan, and several histone deacetylase (HDAC) inhibitors delay Drosophila aging (Kang et al ., 2002;Zhao et al ., 2005). Compounds that extend the lifespan of vertebrates have not been well characterized.…”

p300 plays a role in p16INK4a expression and cell cycle arrest

“…Total cellular RNA was extracted from 293T cells according to the Promega Total RNA Isolation System manual following a previous procedure (Zhao et al, 2005). Samples were analysed by PCR or quantitative PCR.…”