Klotho

Makoto Kuro-O

Research output: Contribution to journalReview article

163 Scopus citations

Abstract

The klotho gene was identified as an "aging-suppressor" gene in mice that accelerates aging when disrupted and extends life span when overexpressed. It encodes a single-pass transmembrane protein and is expressed primarily in renal tubules. The extracellular domain of Klotho protein is secreted into blood and urine by ectodomain shedding. The two forms of Klotho protein, membrane Klotho and secreted Klotho, exert distinct functions. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate co-receptor for FGF23, a bone-derived hormone that induces phosphate excretion into urine. Mice lacking Klotho or FGF23 not only exhibit phosphate retention but also display a premature-aging syndrome, revealing an unexpected link between phosphate metabolism and aging. Secreted Klotho functions as a humoral factor that regulates activity of multiple glycoproteins on the cell surface, including ion channels and growth factor receptors such as insulin/insulin-like growth factor-1 receptors. Potential contribution of these multiple activities of Klotho protein to aging processes is discussed.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalPflugers Archiv European Journal of Physiology
Volume459
Issue number2
DOIs
StatePublished - Jan 1 2010

Keywords

  • FGF23
  • Klotho
  • Phosphate
  • Vitamin D
  • βKlotho

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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