Augmented Wnt signaling in a mammalian model of accelerated aging

被引：599

作者：

Liu, Hongjun

Fergusson, Maria M.

Castilho, Rogerio M.

Liu, Jie

Cao, Liu

Chen, Jichun

Malide, Daniela

Rovira, Ilsa I.

Schimel, Daniel

Kuo, Calvin J.

Gutkind, J. Silvio

Hwang, Paul M.

Finkel, Toren

机构：

[1] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA

[2] Natl Inst Dent & Craniofacial Res, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA

[3] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA

[4] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA

[5] NIH, Mouse Imaging Facil, Bethesda, MD 20892 USA

[6] Stanford Univ, Sch Med, Div Hematol, Stanford, CA 94305 USA

来源：

SCIENCE | 2007年 / 317卷 / 5839期

关键词：

D O I：

10.1126/science.1143578

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：803 / 806

页数：4

共 22 条

[1] Epidermal stem cells of the skin [J].