Augmented Wnt signaling in a mammalian model of accelerated aging

Hongjun Liu, Maria M. Fergusson, Rogerio M. Castilho, Jie Liu, Liu Cao, Jichun Chen, Daniela Malide, Ilsa I. Rovira, Daniel Schimel, Calvin J. Kuo, J. Silvio Gutkind, Paul M. Hwang, Toren Finkel

Research output: Contribution to journalArticlepeer-review

540 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)803-806
Number of pages4
Issue number5839
StatePublished - Aug 10 2007
Externally publishedYes

ASJC Scopus subject areas

  • General


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