It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in Drosophila are affected by whether flies are provided a choice of different nutrients or a single, complete medium, largely independent of the amount of nutrients that are consumed. Meal choice elicits a rapid metabolic reprogramming that indicates a potentiation of TCA cycle and amino acid metabolism, which requires serotonin 2A receptor. Knockdown of glutamate dehydrogenase, a key TCA pathway component, abrogates the effect of dietary choice on lifespan. Our results reveal a mechanism of aging that applies in natural conditions, including our own, in which organisms continuously perceive and evaluate nutrient availability to promote fitness and well-being.
Source data for all quantifications shown in Data Figures 1-5, figures supplements and the supplementary files are provided with the paper. Metabolomic raw data, analyses and statistics can be obtained from Supplementary Files 3-4 and our GitHub repository (github.com/ylyu-fly/Metabolomics-FlyChoiceDiet).
Head and body metabolomes in response to nutrient choiceSupplementary data.
- Yang Lyu
- Kristina J Weaver
- Daniel EL Promislow
- Scott D Pletcher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Meng C Wang, Baylor College of Medicine, HHMI, United States
© 2021, Lyu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.