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Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis
Andrew S. Brack,1Michael J. Conboy,1Sudeep Roy,1Mark Lee,2Calvin J. Kuo,2Charles Keller,3Thomas A. Rando1,4*
The regenerative potential of skeletal muscle declines withage, and this impairment is associated with an increase in tissuefibrosis. We show that muscle stem cells (satellite cells) fromaged mice tend to convert from a myogenic to a fibrogenic lineageas they begin to proliferate and that this conversion is mediatedby factors in the systemic environment of the old animals. Wealso show that this lineage conversion is associated with anactivation of the canonical Wnt signaling pathway in aged myogenicprogenitors and can be suppressed by Wnt inhibitors. Furthermore,components of serum from aged mice that bind to the Frizzledfamily of proteins, which are Wnt receptors, may account forthe elevated Wnt signaling in aged cells. These results indicatethat the Wnt signaling pathway may play a critical role in tissue-specificstem cell aging and an increase in tissue fibrosis with age.
1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. 2 Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA. 4 Geriatric Research, Education, and Clinical Center (GRECC) and Neurology Service, Veterans Affairs (VA) Palo Alto Health Care System, Palo Alto, CA 94304, USA.
* To whom correspondence should be addressed. E-mail: rando{at}stanford.edu
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