Editors' ChoiceMEDICINE
Wnt, the Fountain of Youth?
L. Bryan Ray
Science, Science's STKE, AAAS, Washington, DC 20005, USA
, 's STKE, AAAS, Washington, DC 20005, USA
Wnt proteins are secreted ligands that bind to cell surface receptors and have important effects during development, which it now seems may also contribute to phenotypes of stem and progenitor cells associated with aging. Liu et al. examined stem cell properties in mice carrying a mutation in the Klotho protein, which show characteristics of accelerated aging. They observed increased senescence of stem cells in the mutant mice and found that the Klotho protein physically interacted with and inhibited Wnt proteins in transfected cells. Exposure of mouse embryo fibroblasts in culture to excessive Wnt signaling enhanced senescence, and in transgenic mice it also promoted senescence of skin cells. Brack et al. found that Wnt signaling appeared to be more active in aging animals. Injection of Wnt3A into young regenerating muscle reduced proliferation and increased deposition of connective tissue. Thus, antagonizing Wnt signals could provide a strategy to ease the effects of aging and age-related diseases.
H. Liu, M. M. Fergusson, R. M. Castilho, J. Liu, L. Cao, J. Chen, D. Malide, I. I. Rovira, D. Schimel, C. J. Kuo, J. S. Gutkind, P. M. Hwang, T. Finkel, Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317, 803-806 (2007). [Abstract] [Full Text]
A. S. Brack, M. J. Conboy, S. Roy, M. Lee, C. J. Kuo, C. Keller, T. A. Rando, Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317, 807-810 (2007). [Abstract] [Full Text]
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By L. Bryan Ray
In older mice, overexpression of a signaling pathway may inhibit muscle regeneration by accelerating stem cell senescence while decreasing their proliferation.