Nutrition Forced Extension of Lifespan in Drosophila: A Whole-Genome Investigation

Abstract

The life history trade off between longevity and reproduction is seen in a variety of animals. In the model organism Drosophila melanogaster, regulation of lifespan and reproductive rate are linked to various ratios of protein to carbohydrate diet ingested by the flies throughout their lifetime.

Dietary Restriction and its effects on lifespan has been studied for many years, with consistent results seen between different organisms. Restriction of caloric intake is known to extend lifespan in different organisms. In Drosophila isocaloric diets of yeast (as a protein source) and sugar (as carbohydrate), in varying ratios, results in organisms trading-off lifespan and reproduction, implying macronutrient status rather than caloric restriction extends lifespan.

The aim of the current study is to determine the patterns of gene expression associated with longevity in fruit fly. Drosophila were fed varying ratios of a protein/carbohydrate diet, and whole fly RNA was microarray assayed to identify genes differentially expressed between flies fed high carbohydrates and those fed high protein diets. Differentially expressed genes were verified with Q RT-PCR and a selection of candidate genes were analysed using P element interrupted mutant lines. Immune system stress assays were used to further investigate the response of flies raised on the specified diets.

We show genes annotated as being involved in the immune system and stress response pathways to be significantly differentially expressed in array studies and overrepresented in gene ontology analysis; implying a role in the establishment and control of the lifespan extension phenomenon. We show an absence of significant differential expression in genes previously recorded as being involved in the control of the lifespan extension phenotype, and establish survivorship and lifespan data for a cohort of mutant and control lines.

The current experiment provides direction for new functional assays, and adds to the growing body of knowledge as to what drives the extension of lifespan following dietary restriction.