title: Rpd3interacts with insulin signaling inDrosophilalongevity extension.
abstract: Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and fly HDAC1 orthologue, extends longevity. However, the mechanism ofrpd3's effects on longevity remains unclear. Here we report an overlap betweenrpd3and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways. We demonstrated thatrpd3reduction downregulates expression of members of the IIS pathway, which is associated with altered metabolism, increased energy storage, and higher resistance to starvation and oxidative stress. Genetic studies support the role of IIS inrpd3longevity pathway, as illustrated with reduced stress resistance and longevity of flies double mutant forrpd3anddfoxo,a downstream target of IIS pathway, compared torpd3single mutant flies. Our data suggest that increaseddfoxois a mediator ofrpd3's effects on fly longevity and intermediary metabolism, and confer a new link betweenrpd3and IIS longevity pathways.
authors.affiliation: Department of Genetics & Genome Sciences, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA.
authors.forename: Jared K
authors.initials: JK
authors.lastname: Woods
authors.affiliation: Department of Genetics & Genome Sciences, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA.|current address: Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Health Sciences, McMaster University, Ontario, Canada.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Ziafazeli
authors.affiliation: Department of Genetics & Genome Sciences, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA.|Institute for Systems Genomics, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA.
authors.forename: Blanka
authors.initials: B
authors.lastname: Rogina
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics; D013217:Starvation / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1
keywords: Drosophila melanogaster; Insulin/Insulin-like signaling; Rpd3; aging