Suppression of Aging in Mice by the Hormone Klotho
Hiroshi Kurosu, Masaya Yamamoto, Jeremy D. Clark, Johanne V. Pastor, Animesh Nandi, Prem Gurnani, Owen P. McGuinness, Hirotaka Chikuda, Masayuki Yamaguchi, Hiroshi Kawaguchi, Iichiro Shimomura, Yoshiharu Takayama, Joachim Herz, C. Ronald Kahn, Kevin P. Rosenblatt, Makoto Kuro-o- Multidisciplinary
A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.