1. Rpd3 interacts with insulin signaling in Drosophila longevity extension
- Author
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Tahereh Ziafazeli, Blanka Rogina, and Jared K. Woods
- Subjects
0301 basic medicine ,Aging ,Insulin/Insulin-like signaling ,biology ,media_common.quotation_subject ,Longevity ,Cell Biology ,biology.organism_classification ,Rpd3 ,HDAC1 ,Chromatin ,Cell biology ,03 medical and health sciences ,Longevity Pathway ,Insulin receptor ,Drosophila melanogaster ,030104 developmental biology ,0302 clinical medicine ,Histone ,biology.protein ,Histone deacetylase ,030217 neurology & neurosurgery ,Research Paper ,media_common - 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 of rpd3's effects on longevity remains unclear. Here we report an overlap between rpd3 and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways. We demonstrated that rpd3 reduction 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 in rpd3 longevity pathway, as illustrated with reduced stress resistance and longevity of flies double mutant for rpd3 and dfoxo, a downstream target of IIS pathway, compared to rpd3 single mutant flies. Our data suggest that increased dfoxo is a mediator of rpd3's effects on fly longevity and intermediary metabolism, and confer a new link between rpd3 and IIS longevity pathways.
- Published
- 2016