The epigenetic regulation of DNA structure and function is essential for changes 
in gene expression involved in development, growth, and maintenance of cellular 
function. Epigenetic changes include histone modifications such as methylation, 
acetylation, ubiquitination, and phosphorylation. Histone deacetylase (HDAC) 
proteins have a major role in epigenetic regulation of chromatin structure. 
HDACs are enzymes that catalyze the removal of acetyl groups from lysine 
residues within histones, as well as a range of other proteins including 
transcriptional factors. HDACs are highly conserved proteins divided into two 
families and based on sequence similarity in four classes. Here we will discuss 
the roles of Rpd3 in physiology and longevity with emphasis on its role in 
flies. Rpd3, the Drosophila HDAC1 homolog, is a class I lysine deacetylase and a 
member of a large family of HDAC proteins. Rpd3 has multiple functions including 
control of proliferation, development, metabolism, and aging. Pharmacological 
and dietary HDAC inhibitors have been used as therapeutics in psychiatry, 
cancer, and neurology.