Genetic and environmental variation in the effect of dietary restriction on life-history trade-offs and ageing in Drosophila

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Understanding the causes and consequences of variation in longevity and ageing is important not only in the context of life history evolution, but also in our attempts to understand and mitigate these processes in humans. Life history theory predicts that variation in longevity and ageing is related to the trade-off between survival and reproduction. Dietary restriction (DR), a modest reduction in nutrient intake, has been shown to increase longevity and slow rates of ageing across a diverse range of species. The evolutionary explanation for this prolongevity effect of DR is that it alters the trade-off between survival and reproduction in the favour of increased investment in survival. Although the effect of DR is thought to be evolutionarily conserved, recent studies suggest genetic variation in the response to DR. In addition, recent theory has questioned whether the prolongevity and anti-ageing effect of DR will persist when organisms are exposed to ecologically relevant stressors such as pathogens, physical injury and temperature variation. Understanding the extent of this variation in the response of longevity and ageing to diet is clearly important in improving our understanding of the ageing process, how it might be mediated by diet and how this may vary between individuals and environments. This project will use Drosophila melanogaster as a model organism in which to provide detailed studies of genetic variation in the response to DR and the effect of exposure to environmental stress.

Drosophila will be reared on diets that differ in yeast content and the effect of these diets on longevity, reproduction and ageing in various traits will be assessed. Using the Drosophila Genetic Reference Panel (DGRP) (~ 200 inbred lines of Drosophila), quantitative genetic experiments will be performed to allow estimation of the quantitative genetic variation in the response to DR and how DR influences the genetic (co)variation between life history traits; a key measure of life history trade-offs. The existence of genome wide sequence data for these lines will allow investigation of candidate genes underlying this variation. In addition, Drosophila on different diets will be exposed to environmental stressors including pathogens, physical injury and temperature variation to assess the effect of environmental variation on the response to DR. This PhD will provide training in the design, implementation and analysis of complex experiments across multiple generations as well as learning techniques for assaying and analysing traits such as growth, survival, physical performance etc. In addition, Drosophila melanogaster represent an incredibly well studied and flexible system that will allow a student scope to develop their own ideas.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M010996/1 01/10/2015 31/03/2024
1869155 Studentship BB/M010996/1 01/10/2016 31/12/2020
 
Description The work involved with this award has shown that with additional stressors of infection and injury, dietary restriction (DR) responses remain in more stressful environments compared to the usual benign laboratory conditions in a commonly tested laboratory organism, fruit flies (Drosophila melanogaster). Here, DR was achieved through changes in the protein to non-protein content of food (through changes in yeast to sugar ratios), whilst not changing the caloric value of the food. In addition, changes in larval macronutrient were not found to affect adult lifespan, when adult diet was kept constant, and importantly, did not alter survival post-infection in adulthood with the same pathogen. Larval diet higher in protein:carbohydrate (P:C) increased successful development to adulthood and adults had higher early-life reproduction, and development was quickest on intermediate P:C. Although survival post-infection using this particular pathogen was higher on higher P:C, we found no evidence that infected individuals changed their short-term food choice post-infection to favor a diet with a protein source, as previously seen with other pathogens. Finally, there was no change in how individuals were able to control the bacterial growth post-infection or in their production of antimicrobial peptide production, however this requires further study to understand these changes in the host and pathogen dynamics post-infection with this pathogen.
Exploitation Route Further research should focus on understanding these interactions further by the use of different pathogens or methods of infection, to understand whether these patterns in lifetime life-history traits are present or to determine how they change with variation in methods. Additionally, further experiments should include diets which vary in both calories and nutrients to understand how the interplay in the complexity of diets change these patterns, or whether they remain similar across such interactions.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology