Serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice
- University of Michigan, United States
- University of Washington, United States
Abstract
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.
Data availability
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).
Article and author information
Author details
Funding
Burroughs Wellcome Fund (Collaborative Research Travel Grant,BWF1017452)
- Yang Lyu
National Science Foundation (Graduate Research Fellowship Program,DGE 1256260)
- Kristina J Weaver
National Institutes of Health (R01 AG049494 and P30 AG013280)
- Daniel EL Promislow
National Institutes of Health (R01 AG051649 and R01 AG030593)
- Scott D Pletcher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 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.
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Serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice
eLife 10:e59399.
https://doi.org/10.7554/eLife.59399
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