Klotho

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.