Suppression of aging in mice by the hormone Klotho

Science. 2005 Sep 16;309(5742):1829-33. doi: 10.1126/science.1112766. Epub 2005 Aug 25.

Abstract

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

Publication types

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

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Blood Glucose / analysis
  • Cell Line
  • Cell Line, Tumor
  • Eating
  • Female
  • Glucuronidase
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Ligands
  • Longevity / genetics
  • Longevity / physiology*
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / pharmacology
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Myoblasts / metabolism
  • Oxygen Consumption
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Phosphorylation
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / metabolism
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Signal Transduction

Substances

  • Blood Glucose
  • Insulin
  • Ligands
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Glucuronidase
  • klotho protein