Augmented Wnt Signaling in a Mammalian Model of Accelerated Aging-Reference-Cited by-同舟云学术

Augmented Wnt Signaling in a Mammalian Model of Accelerated Aging

Published:2007-08-10 Issue:5839 Volume:317 Page:803-806
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Liu Hongjun¹²³⁴⁵,Fergusson Maria M¹²³⁴⁵,Castilho Rogerio M.¹²³⁴⁵,Liu Jie¹²³⁴⁵,Cao Liu¹²³⁴⁵,Chen Jichun¹²³⁴⁵,Malide Daniela¹²³⁴⁵,Rovira Ilsa I.¹²³⁴⁵,Schimel Daniel¹²³⁴⁵,Kuo Calvin J.¹²³⁴⁵,Gutkind J. Silvio¹²³⁴⁵,Hwang Paul M.¹²³⁴⁵,Finkel Toren¹²³⁴⁵

Affiliation:

1. Cardiology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.

2. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.

3. Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.

4. Light Microscopy Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.

5. Mouse Imaging Facility, NIH, Bethesda, MD 20892, USA.

Abstract

The contribution of stem and progenitor cell dysfunction and depletion in normal aging remains incompletely understood. We explored this concept in the Klotho mouse model of accelerated aging. Analysis of various tissues and organs from young Klotho mice revealed a decrease in stem cell number and an increase in progenitor cell senescence. Because klotho is a secreted protein, we postulated that klotho might interact with other soluble mediators of stem cells. We found that klotho bound to various Wnt family members. In a cell culture model, the Wnt-klotho interaction resulted in the suppression of Wnt biological activity. Tissues and organs from klotho-deficient animals showed evidence of increased Wnt signaling, and ectopic expression of klotho antagonized the activity of endogenous and exogenous Wnt. Both in vitro and in vivo, continuous Wnt exposure triggered accelerated cellular senescence. Thus, klotho appears to be a secreted Wnt antagonist and Wnt proteins have an unexpected role in mammalian aging.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference24 articles.

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4. Materials and methods are available as supporting material on Science Online.

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