Klotho and aging

Makoto Kuro-o

Research output: Contribution to journalReview articlepeer-review

204 Scopus citations

Abstract

The klotho gene encodes a single-pass transmembrane protein that forms a complex with multiple fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for FGF23, a bone-derived hormone that induces negative phosphate balance. Defects in either Klotho or Fgf23 gene expression cause not only phosphate retention but also a premature-aging syndrome in mice, unveiling a potential link between phosphate metabolism and aging. In addition, the extracellular domain of Klotho protein is clipped on the cell surface and secreted into blood stream, potentially functioning as an endocrine factor. The secreted Klotho protein has a putative sialidase activity that modifies glycans on the cell surface, which may explain the ability of secreted Klotho protein to regulate activity of multiple ion channels and growth factors including insulin, IGF-1, and Wnt. Secreted Klotho protein also protects cells and tissues from oxidative stress through a mechanism yet to be identified. Thus, the transmembrane and secreted forms of Klotho protein have distinct functions, which may collectively affect aging processes in mammals.

Original languageEnglish (US)
Pages (from-to)1049-1058
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number10
DOIs
StatePublished - Oct 1 2009

Keywords

  • FGF23
  • Klotho
  • Phosphate
  • Sialidase
  • TRPV5
  • Vitamin D

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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