Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice
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
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.
Reviewing Editor
- Weiwei Dang, Baylor College of Medicine, United States
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).
Version history
- Received: August 26, 2020
- Accepted: March 16, 2021
- Accepted Manuscript published: March 30, 2021 (version 1)
- Version of Record published: March 30, 2021 (version 2)
- 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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