The Mechanism of Life Span Extension in rpd3-mutant Drosophila

It was previously discovered that mutations in rpd3, a gene coding for the mammalian histone deacetylase 1 (HDAC1) homologue, led to an increased lifespan in Drosophila (Rogina et al., 2002). From changes in dSir2 gene expression observed in this initial study and the fact that flies on a calorically restricted diet did not live longer, it was hypothesized that the mechanism of longevity extension overlapped with that of caloric restriction (CR). CR is one of the most effective ways to extend life span in a variety of species ranging from yeast to mammals. CR affects many aspects of metabolism including mitochondrial function, the insulin signaling pathway, and the TOR signaling pathway. Because of this, we investigated these pathways in rpd3-mutant Drosophila. Our results indicated that there are no changes in mitochondrial biogenesis, but small changes in mitochondrial function may exist. Interestingly, we saw a decrease in the insulin signaling pathway that suggests insulin signaling may mediate some of the effects observed in rpd3 mutants. In addition we performed mRNA sequencing and determined that there may be changes in the innate immune system of rpd3 mutants. We also provide a protocol for the measurement of spontaneous locomotor activity in Drosophila (Woods et al., 2014). Taken together, these results provide insight into the pathways involved in life span extension in rpd3-mutant Drosophila