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Cell biology

Klotho

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Klotho (here referring to alpha-Klotho, distinct from beta-Klotho) is a transmembrane protein, predominantly expressed in the kidney and brain, that also circulates as a soluble hormone after cleavage. It regulates phosphate and vitamin D homeostasis via FGF23 co-receptor function and modulates several signaling pathways including insulin/IGF-1, Wnt, and others. Klotho-deficient mice show accelerated aging phenotypes, while Klotho overexpression extends lifespan. Higher circulating Klotho levels in humans are associated with better cognitive performance and reduced cardiovascular and renal disease risk.

Sources

  1. Kuro-o M, Matsumura Y, Aizawa H, et al.. (1997). Mutation of the mouse klotho gene leads to a syndrome resembling ageing. *Nature*doi:10.1038/36285
  2. Hu MC, Shi M, Zhang J, et al.. (2010). Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. *FASEB Journal*doi:10.1096/fj.10-154765
  3. Kurosu H, Yamamoto M, Clark JD, et al.. (2005). Suppression of aging in mice by the hormone Klotho. *Science*doi:10.1126/science.1112766