Both groups chanced on the connection to Wnt, whose many functions include promoting differentiation and cell division. Hongjun Liu, Toren Finkel (National Heart, Lung, and Blood Institute, Bethesda, MD), and colleagues were studying mice that lack the protein klotho. The animals die young after showing signs of premature aging such as hardened arteries. The researchers detected a surge in cellular senescence in locations where stem cells are proliferating, such as the skin, small intestine, and bone marrow.
Klotho and Wnt proteins are antagonists, the scientists found. Adding klotho to cultured cells quashed Wnt activity. Moreover, Wnt pushed mouse embryonic fibroblasts to senesce, but extra klotho countered the effect. Overall, the work indicates that, by boosting senescence, Wnt spurs animals to fritter away their stem cells.
Andrew Brack, Tom Rando (Stanford University, Stanford, CA), and colleagues report similar results for satellite cells. These cells normally mend damaged muscle, but as we get older, they often start producing tough fibers instead of fresh muscle cells. Wnt spurs other cell types to morph into fiber-manufacturing cells, and the researchers determined that the pathway did the same to muscle. Adding Wnt3A to young satellite cells, for example, caused more to convert into fiber makers.
The results held true in vivo. Injecting Wnt3A into injured muscles of young mice slowed cell division and boosted fiber formation. The scientists also found that, in older mice, Wnt signaling in satellite cells climbed. The findings suggest that Wnt undermines our muscles' capacity for repair as we age.