Authors: Kurosu H; Yamamoto M; Clark JD; Pastor JV; Nandi A; Gurnani P; McGuinness OP; Chikuda H; Yamaguchi M; Kawaguchi H; Shimomura I; Takayama Y; Herz J; Kahn CR; Rosenblatt KP; Kuro-o M
Abstract: 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.Keywords: Aging/genetics/*physiology; Animals; Blood Glucose/analysis; Cell Line; Cell Line, Tumor; Eating; Female; Glucuronidase; Insulin/blood/metabolism; Insulin Resistance; Insulin-Like Growth Factor I/metabolism/pharmacology; Ligands; Longevity/genetics/*physiology; Male; Membrane Proteins/chemistry/*genetics/pharmacology/*physiology; Mice; Mice, Transgenic; Myoblasts/metabolism; Oxygen Consumption; Peptide Fragments/chemistry/pharmacology; Phosphorylation; Receptor, IGF Type 1/metabolism; Receptor, Insulin/metabolism; Receptors, Cell Surface/metabolism; Recombinant Proteins/chemistry/isolation & purification/metabolism; Signal Transduction
Journal: Science (New York, N.Y.)
Date: Aug. 27, 2005
Select reference article to upload
Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M (2005) Suppression of aging in mice by the hormone Klotho. Science (New York, N.Y.) 309: 1829-33.