Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis

Andrew S. Brack, Michael J. Conboy, Sudeep Roy, Mark Lee, Calvin J. Kuo, Charles Keller, Thomas A. Rando

    Research output: Contribution to journalArticlepeer-review

    974 Scopus citations

    Abstract

    The regenerative potential of skeletal muscle declines with age, and this impairment is associated with an increase in tissue fibrosis. We show that muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate and that this conversion is mediated by factors in the systemic environment of the old animals. We also show that this lineage conversion is associated with an activation of the canonical Wnt signaling pathway in aged myogenic progenitors and can be suppressed by Wnt inhibitors. Furthermore, components of serum from aged mice that bind to the Frizzled family of proteins, which are Wnt receptors, may account for the elevated Wnt signaling in aged cells. These results indicate that the Wnt signaling pathway may play a critical role in tissue-specific stem cell aging and an increase in tissue fibrosis with age.

    Original languageEnglish (US)
    Pages (from-to)807-810
    Number of pages4
    JournalScience
    Volume317
    Issue number5839
    DOIs
    StatePublished - Aug 10 2007

    ASJC Scopus subject areas

    • General

    Fingerprint

    Dive into the research topics of 'Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis'. Together they form a unique fingerprint.

    Cite this