Suppression of Aging in Mice by the Hormone Klotho-Reference-Cited by-同舟云学术

Suppression of Aging in Mice by the Hormone Klotho

Published:2005-09-16 Issue:5742 Volume:309 Page:1829-1833
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kurosu Hiroshi¹²³⁴⁵,Yamamoto Masaya¹²³⁴⁵,Clark Jeremy D.¹²³⁴⁵,Pastor Johanne V.¹²³⁴⁵,Nandi Animesh¹²³⁴⁵,Gurnani Prem¹²³⁴⁵,McGuinness Owen P.¹²³⁴⁵,Chikuda Hirotaka¹²³⁴⁵,Yamaguchi Masayuki¹²³⁴⁵,Kawaguchi Hiroshi¹²³⁴⁵,Shimomura Iichiro¹²³⁴⁵,Takayama Yoshiharu¹²³⁴⁵,Herz Joachim¹²³⁴⁵,Kahn C. Ronald¹²³⁴⁵,Rosenblatt Kevin P.¹²³⁴⁵,Kuro-o Makoto¹²³⁴⁵

Affiliation:

1. Department of Pathology, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.

2. Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.

3. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, Tennessee 37232-0615, USA.

4. Department of Sensory and Motor System Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

5. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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