Suppression of Aging in Mice by the Hormone Klotho

作者：Hiroshi Kurosu, Masaya Yamamoto, Jeremy D. Clark, Johanne Virginia 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 · 发表于：Science · 年份：2005 · DOI：10.1126/science.1112766 · 被引用次数：1956 · 研究领域：Parathyroid Disorders and Treatments、Genetic Syndromes and Imprinting、Birth, Development, and Health

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.