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