1. Biochemistry and Chemical Biology
  2. Genetics and Genomics
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Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice

  1. Jason D Plummer
  2. Spike DL Postnikoff
  3. Jessica K Tyler
  4. Jay E Johnson  Is a corresponding author
  1. Orentreich Foundation for the Advancement of Science, United States
  2. Weill Cornell Medicine, United States
Research Article
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Cite this article as: eLife 2021;10:e62483 doi: 10.7554/eLife.62483

Abstract

Methionine restriction (MR) dramatically extends the healthspan of several organisms. Methionine-restricted rodents have less age-related pathology and increased longevity as compared with controls, and recent studies suggest that humans might benefit similarly. Mechanistically, it is likely that the decreased IGF-1 signaling that results from MR underlies the benefits of this regimen. Thus, we hypothesized that interventions that decrease IGF-1 signaling would also produce MR-like healthspan benefits. Selenium supplementation inhibits IGF-1 signaling in rats, and has been studied for its putative healthspan benefits. Indeed, we show that feeding mice a diet supplemented with sodium selenite results in an MR-like phenotype, marked by protection against diet-induced obesity, as well as altered plasma levels of IGF-1, FGF-21, adiponectin, and leptin. Selenomethionine supplementation results in a similar, albeit less robust response, and also extends budding yeast lifespan. Our results indicate that selenium supplementation is sufficient to produce MR-like healthspan benefits for yeast and mammals.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jason D Plummer

    Biology, Orentreich Foundation for the Advancement of Science, Cold Spring, United States
    Competing interests
    No competing interests declared.
  2. Spike DL Postnikoff

    Pathology and Lab Medicine, Weill Cornell Medicine, New York, United States
    Competing interests
    No competing interests declared.
  3. Jessica K Tyler

    Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
    Competing interests
    Jessica K Tyler, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9765-1659
  4. Jay E Johnson

    Biology, Orentreich Foundation for the Advancement of Science, Cold Spring, United States
    For correspondence
    jjohnson@orentreich.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1267-7575

Funding

Orentreich Foundation for the Advancement of Science (CCL023-CCL025)

  • Jay E Johnson

National Institutes of Health (R01 AG050660)

  • Jessica K Tyler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of the Orentreich Foundation for the Advancement of Science, Inc. (Permit Number: 0511MB).

Reviewing Editor

  1. Weiwei Dang, Baylor College of Medicine, United States

Publication history

  1. Received: August 26, 2020
  2. Accepted: March 16, 2021
  3. Accepted Manuscript published: March 30, 2021 (version 1)
  4. Version of Record published: March 30, 2021 (version 2)
  5. Version of Record updated: August 4, 2021 (version 3)

Copyright

© 2021, Plummer 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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