Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Genetic studies of single gene mutations are revealing mechanisms and pathways that regulate longevity across distant species. One such mechanism is an alteration in histone deacetylase activity. Abolishing expression of the Rpd3 deacetylase or increasing expression of the Sir2 deacetylase increases life-span in yeast; Sir2 mediates increased nematode longevity as well. Caloric restriction is an intervention that increases life-span in mammals, insects, nematodes, and yeast. Although the molecular pathways underlying the response to caloric restriction are yielding to genetic analysis in yeast, there is little information on how this response is regulated in metazoans. We investigated the relationship between histone deacetylases, caloric restriction, and longevity in Drosophila.