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.
- 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
- Received: May 28, 2020
- Accepted: January 4, 2021
- Accepted Manuscript published: January 19, 2021 (version 1)
© 2021, Lyu et al.
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