DOI: 10.1126/science.1144090. Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis

Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis

10.1126/science.1144090

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

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), 807â810.

Authors 7

Andrew S. Brack (first)
Michael J. Conboy (additional)
Sudeep Roy (additional)
Mark Lee (additional)
Calvin J. Kuo (additional)
Charles Keller (additional)
Thomas A. Rando (additional)

References 19 Referenced 1,279

10.1016/0960-8966(94)90019-1
10.1111/j.1749-6632.1998.tb09894.x
10.4161/cc.4.3.1518
10.1016/0022-510X(94)00276-T
10.1126/science.1087573
10.1038/nature03260
Materials and methods are available as supporting material on Science Online.
10.1016/S0002-9440(10)64282-4
10.1016/j.jhep.2006.03.016
10.1128/MCB.22.4.1172-1183.2002
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10.1073/pnas.2536800100
10.1186/1471-2121-7-28
10.1126/science.1143578
10.1038/sj.cr.7290260
10.1002/dvdy.20672
We thank E. Fuchs for TOPGAL mice R. Nusse for recombinant Wnt3A and LSL cells and B. Olwin for the Syndecan-4 antibody. Supported by a grant from the NIH (DK069989) to C.J.K. and by grants from the NIH (AG23806) the Department of Veterans Affairs (Merit Review) the Ellison Medical Foundation and an NIH Director's Pioneer Award to T.A.R.

Dates

Type	When
Created	18 years ago (Aug. 9, 2007, 4:39 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 4:38 a.m.)
Indexed	49 minutes ago (Aug. 30, 2025, 2:45 a.m.)
Issued	18 years ago (Aug. 10, 2007)
Published	18 years ago (Aug. 10, 2007)
Published Print	18 years ago (Aug. 10, 2007)

Funders 0

None

BibTeX

@article{Brack_2007, title={Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis}, volume={317}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1144090}, DOI={10.1126/science.1144090}, number={5839}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Brack, Andrew S. and Conboy, Michael J. and Roy, Sudeep and Lee, Mark and Kuo, Calvin J. and Keller, Charles and Rando, Thomas A.}, year={2007}, month=aug, pages={807–810} }

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