Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice

Elife. 2021 Mar 30;10:e62483. doi: 10.7554/eLife.62483.


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.

Keywords: S. cerevisiae; aging; biochemistry; chemical biology; genetics; genomics; histone deacetylase; lifespan; metabolism; mitophagy; mouse; selenomethionine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed / analysis
  • Animals
  • Diet
  • Dietary Supplements / analysis
  • Dose-Response Relationship, Drug
  • Female
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Methionine / administration & dosage*
  • Mice / physiology*
  • Mice, Inbred C57BL
  • Random Allocation
  • Selenium / administration & dosage
  • Selenium / metabolism*
  • Selenomethionine / administration & dosage
  • Selenomethionine / metabolism*
  • Sodium Selenite / administration & dosage
  • Sodium Selenite / metabolism*


  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • Selenomethionine
  • Methionine
  • Selenium
  • Sodium Selenite