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Related Experiment Video

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A Simple Mechanical Procedure to Create Limbal Stem Cell Deficiency in Mouse
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Selenium Deficiency Is Associated with Pro-longevity Mechanisms.

Sun Hee Yim1, Clary B Clish2, Vadim N Gladyshev1

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Cell Reports
|May 30, 2019
PubMed
Summary

Selenium deficiency surprisingly results in normal lifespan in mice by altering metabolism. This involves reduced amino acids and activated nutrient-sensing pathways, compensating for lost selenoprotein functions.

Keywords:
aginggene expressionlifespanmetabolic pathwaymetabolite profilingmiRNAnutritionseleniumselenoproteinstranscriptome

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Area of Science:

  • Biochemistry
  • Nutritional Science
  • Genomics

Background:

  • Selenium (Se) is vital for selenoproteins, impacting redox homeostasis.
  • Both Se deficiency and excess Se are linked to adverse health outcomes.
  • Se deficiency drastically reduces selenoprotein expression.

Purpose of the Study:

  • Investigate the molecular mechanisms behind normal lifespan in Se-deficient mice.
  • Understand how metabolic adaptations compensate for reduced selenoprotein function.
  • Explore the role of nutrient-sensing pathways in Se deficiency.

Main Methods:

  • Systemic analyses including metabolome, transcriptome, and microRNA profiling.
  • Lifespan studies in mice subjected to lifelong Se-deficient diets.
  • Comparative analysis of metabolic and signaling pathway alterations.

Main Results:

  • Se deficiency led to reduced amino acid levels and elevated mononucleotides.
  • Metabolic alterations and activation of longevity-related nutrient-sensing pathways were observed.
  • Despite drastically reduced selenoprotein expression, mice exhibited normal lifespans.

Conclusions:

  • Metabolic control and nutrient sensing pathways adapt to Se deficiency.
  • These adaptations compensate for suppressed selenoprotein functions.
  • This coordinated response ensures a normal lifespan even with Se deficiency.