1. Genetics and Genomics
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Serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice

  1. Yang Lyu
  2. Kristina J Weaver
  3. Humza A Shaukat
  4. Marta L Plumoff
  5. Maria Tjilos
  6. Daniel EL Promislow
  7. Scott D Pletcher  Is a corresponding author
  1. University of Michigan, United States
  2. University of Washington, United States
Research Article
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Cite this article as: eLife 2021;10:e59399 doi: 10.7554/eLife.59399

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).

The following data sets were generated

Article and author information

Author details

  1. Yang Lyu

    Molecuar and Integrative Physiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4618-9043
  2. Kristina J Weaver

    Molecuar and Integrative Physiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Humza A Shaukat

    College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Marta L Plumoff

    College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria Tjilos

    College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel EL Promislow

    Department of Lab Medicine & Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Scott D Pletcher

    Molecuar and Integrative Physiology, University of Michigan, Ann Arbor, United States
    For correspondence
    spletch@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4812-3785

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.

Reviewing Editor

  1. Meng C Wang, Baylor College of Medicine, HHMI, United States

Publication history

  1. Received: May 28, 2020
  2. Accepted: January 4, 2021
  3. Accepted Manuscript published: January 19, 2021 (version 1)
  4. Version of Record published: February 26, 2021 (version 2)

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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