Klotho as a regulator of oxidative stress and senescence

Makoto Kuro-o

Research output: Contribution to journalReview article

181 Scopus citations

Abstract

The klotho gene functions as an aging-suppressor gene that extends life span when overexpressed and accelerates aging-like phenotypes when disrupted in mice. The klotho gene encodes a single-pass transmembrane protein that binds to multiple fibroblast growth factor (FGF) receptors and functions as a co-receptor for FGF23, a bone-derived hormone that suppresses phosphate reabsorption and vitamin D biosynthesis in the kidney. In addition, the extracellular domain of Klotho protein is shed and secreted, potentially functioning as a humoral factor. The secreted Klotho protein can regulate multiple growth factor signaling pathways, including insulin/IGF-1 and Wnt, and the activity of multiple ion channels. Klotho protein also protects cells and tissues from oxidative stress, yet the precise mechanism underlying these activities remains to be determined. Thus, understanding of Klotho protein function is expected to provide new insights into the molecular basis for aging, phosphate/vitamin D metabolism, cancer and stem cell biology.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalBiological Chemistry
Volume389
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Fibroblast growth factor (FGF)
  • IGF
  • Phosphate
  • Vitamin D
  • Wnt

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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