Department of Pathology, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.
Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, Tennessee 37232-0615, USA.
Department of Sensory and Motor System Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
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.