KLOTHO is the systemic anti-aging hormone within the glycosidase1 superfamily. It encodes a type I membrane protein that is abundant in the kidney and brain. In mice, a deficiency in KLOTHO expression leads to various systemic phenotypes resembling human aging such as arteriosclerosis, osteoporosis, and skin atrophy together with growth retardation, short life-span and infertility. Transgenic mice overexpressing KLOTHO have an extended life span by inhibiting insulin/IGF1 signaling. KLOTHO is involved in the regulation of calcium/phosphorus homeostasis by inhibiting the synthesis of active vitamin D and identified as a potential tumor suppressor.
