Research Paper Volume 7, Issue 12 pp 1112—1128
RPD3 histone deacetylase and nutrition have distinct but interacting effects on Drosophila longevity
- 1 Department of Biology, University of Hartford, West Hartford, CT 06117, USA
- 2 Department of Genetics & Genome Sciences, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA
- 3 Institute for Systems Genomics, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA
- 4 Current address: Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Health Sciences, McMaster University, Ontario, Canada
Received: September 19, 2015 Accepted: November 29, 2015 Published: December 8, 2015https://doi.org/10.18632/aging.100856
How to Cite
Copyright: © 2022 Frankel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Single-gene mutations that extend longevity have revealed regulatory pathways related to aging and longevity. RPD3 is a conserved histone deacetylase (Class I HDAC). Previously we showed that Drosophila rpd3 mutations increase longevity. Here we tested the longevity effects of RPD3 on multiple nutrient levels. Dietary restriction (DR) has additive effects on RPD3-mediated longevity extension, but the effect may be modestly attenuated relative to controls. RPD3 and DR therefore appear to operate by distinct but interacting mechanisms. Since RPD3 regulates transcription, the mRNA levels for two proteins involved in nutrient signaling, 4E-BP and Tor, were examined in rpd3 mutant flies. 4E-BP mRNA was reduced under longevity-increasing conditions. Epistasis between RPD3 and 4E-BP with regard to longevity was then tested. Flies only heterozygous for a mutation in Thor, the 4E-BP gene, have modestly decreased life spans. Flies mutant for both rpd3 and Thor show a superposition of a large RPD3-mediated increase and a small Thor-mediated decrease in longevity at all food levels, consistent with each gene product having distinct effects on life span. However, DR-mediated extension was absent in males carrying both mutations and lessened in females. Our results support the view that multiple discrete but interacting mechanisms regulate longevity.