Klotho as a regulator of oxidative stress and senescence

Biol Chem. 2008 Mar;389(3):233-41. doi: 10.1515/BC.2008.028.


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.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Atrophy / pathology
  • Bone Density
  • Calcinosis / pathology
  • Cognition Disorders / etiology
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / physiology
  • Glucuronidase / genetics
  • Glucuronidase / physiology*
  • Hearing Loss / etiology
  • Hypogonadism / pathology
  • Insulin / physiology
  • Insulin-Like Growth Factor I / physiology
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Klotho Proteins
  • Male
  • Mice
  • Mice, Transgenic
  • Nitric Oxide / biosynthesis
  • Osteoporosis / physiopathology
  • Oxidative Stress / drug effects*
  • Pulmonary Emphysema / etiology
  • Signal Transduction / drug effects
  • Skin / pathology
  • Spinal Cord Diseases / etiology
  • Wnt Proteins / drug effects
  • Wnt Proteins / physiology


  • Fgf23 protein, mouse
  • Insulin
  • Ion Channels
  • Wnt Proteins
  • Nitric Oxide
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins