Klotho: bone, kidney, vascular calcifications, and the aging process

Klotho protein, originally identified as a product of the aging suppressor gene, functions in the kidney as an obligatory co-receptor for FGF23, a bone-derived hormone that suppresses renal phosphate reabsorption and vitamin D synthesis. In addition, the extracellular domain of Klotho protein is clipped on the cell surface and released into systemic circulation. The secreted Klotho functions as a kidney-derived endocrine factor that regulates activity of multiple cell-surface glycoproteins including ion channels and growth factor receptors in various tissues. These diverse activities of membrane and secreted Klotho protein collectively contributes to anti-aging properties of Klotho, including reduction of oxidative stress, prevention of vascular calcification, and preservation of renal function.