Food for Thought: Can Intermittent Fasting Ameliorate Dementia in D. Melanogaster?

Overview

Background: Dementia is highly prevalent neuropsychiatric condition characterized by impairments in memory, reasoning, mood, and behavior. Yet it has no effective treatment that targets the underlying biochemical pathology. The main goals of this project were to utilize a Drosophila melanogaster model of Dementia and determine whether ketosis induced by intermittent time-restricted feeding (iTRF) can lead to decreased mortality, improved memory, and enhanced locomotor function. Methods: flies with the V337M Tau mutation were used as a validated model of dementia. Both demented and control flies were subjected to either: (a) 24 hours access to food/ad libitum or ad lib OR (b) a Time Restricted Feeding (TRF) schedule with 10 hours of fasting during lights off and 14 hours of access to food, mostly during lights on. To assess the effect on lifespan, the percent of flies surviving over time, within each group, was calculated. Impaired geotaxis, diminished climbing motivation and ability, was assessed as a measure of locomotor ability. The Aversive phototaxic suppression assay was used to assess learning/memory; flies learned to avoid light that is paired with an aversive stimulus. Group differences were analyzed with survival curves. Chi-square tests were used for the categorical variables. Results: Survival curve analysis showed that the flies subjected to iTRF for 4 days lived longer than flies who fed ad lib, with the effect being more pronounced among the dementia group. Flies with Dementia had impaired climbing ability compared with controls, but within each group, there was no significant difference in locomotor function, among those fed ad lib versus iTRF. Flies with dementia demonstrated significant impairment in short-term memory and learning compared to the control flies (p-value = 0.03). iTRF did not improve short-term memory among control flies (p-value = 0.55) but greatly enhanced memory and learning in the dementia group (p-value = 0.04). Conclusion: Intermittent Time Restricted Feeding, and associated ketosis, may be a promising new intervention for dementia. Future studies should evaluate the underlying metabolic pathways as well as the changes in brain pathology that accompany improvement in clinical symptoms.