Investigating the role of nutrient sensing signalling pathways and diet in brain ageing in Drosophila melanogaster

The nutrient sensing pathways, insulin/IGF-like (IIS) and TOR signalling, are involved in multiple processes including ageing. Reduced IIS or TOR signalling can extend lifespan and improve some aspects of health at older ages in laboratory model organisms such as worms, flies and mice, and recent studies suggest these pathways are also involved in human ageing. They are thus being investigated as potential therapeutic targets for treating ageing-related functional and health declines in humans. However, we know very little about the effect of these pathways and lifespan-extending manipulations on brain ageing and the cognitive and behavioural declines that occur during normal ageing. To investigate the role of these pathways and their interaction with diet in brain ageing, IIS or TOR mutant Drosophila melanogaster under different dietary regimes will be analysed throughout life. Brain ageing in these flies will be assessed using: (1) behavioural senescence as a functional measure of brain ageing; and (2) central nervous system anatomy and neurodegeneration as a structural measure of brain ageing. The behavioural phenotypes that will be assessed throughout life will include exploratory walking, learning and memory, and sleep, behaviours which decline with age in flies similarly to humans.