Wong, R.; (2009) Epic studies of dietary restriction, feeding behaviour and insulin signalling in the fruit fly, Drosophila melanogaster. Doctoral thesis , UCL (University College London).

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Abstract

Dietary restriction (DR) extends lifespan in many organisms, through unknown mechanisms that may or may not be evolutionarily conserved. Currently, different diets and techniques exist in different laboratories to implement DR in the fruit fly, Drosophila melanogaster. Furthermore, DR is often implemented by food dilution, a technique that potentially enables flies to compensate for reduced nutrition by increasing their food intake. Thus, findings from DR experiments may not be strictly comparable because of these methodological differences and uncertainties. In this thesis, I examined the ability of DR to extend life in D. melanogaster with different genotypes and on different diet compositions. I demonstrate that many of the different diets used in different laboratories are inappropriate for DR and propose an optimised protocol to insure that DR studies are standardised. I also demonstrate, by combining two available feeding assays, that D. melanogaster do not compensate their food intake when exposed to DR by food dilution. The optimised feeding assay in this thesis provides a useful tool for researchers to measure fly total feeding, which is fundamental to studies involving their behaviour, nutrition and/ or drug administration. I demonstrate with this method that food intake is not altered in the lifespan extending mutation chico, the receptor substrate of the insulin/insulin-like signaling (IIS) pathway. IIS is a highly conserved pathway responsible for growth, development, stress resistance, metabolic homeostasis, reproduction, and recently, single gene mutations in the pathway have been shown to extend lifespan. One component of the pathway, dAkt, has yet to be established as a regulator of lifespan and fecundity in D. melanogaster. Although there is sufficient literature regarding its role in growth and development in fly larvae, it is much less understood in adults. Using viable dAkt mutants, I establish that for lifespan benefits to occur, the appropriate level of IIS reduction is required.

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