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 journalArticle

843 Citations (Scopus)

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
Externally publishedYes

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Wnt Signaling Pathway
Muscle Cells
Fibrosis
Stem Cells
Wnt Receptors
Frizzled Receptors
Cell Aging
Skeletal Muscle
Serum

ASJC Scopus subject areas

  • General

Cite this

Brack, A. S., Conboy, M. J., Roy, S., Lee, M., Kuo, C. J., Keller, C., & Rando, T. A. (2007). Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science, 317(5839), 807-810. https://doi.org/10.1126/science.1144090

Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. / Brack, Andrew S.; Conboy, Michael J.; Roy, Sudeep; Lee, Mark; Kuo, Calvin J.; Keller, Charles; Rando, Thomas A.

In: Science, Vol. 317, No. 5839, 10.08.2007, p. 807-810.

Research output: Contribution to journalArticle

Brack, AS, Conboy, MJ, Roy, S, Lee, M, Kuo, CJ, Keller, C & Rando, TA 2007, 'Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis', Science, vol. 317, no. 5839, pp. 807-810. https://doi.org/10.1126/science.1144090
Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007 Aug 10;317(5839):807-810. https://doi.org/10.1126/science.1144090
Brack, Andrew S. ; Conboy, Michael J. ; Roy, Sudeep ; Lee, Mark ; Kuo, Calvin J. ; Keller, Charles ; Rando, Thomas A. / Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. In: Science. 2007 ; Vol. 317, No. 5839. pp. 807-810.
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