Cell Reports
Volume 18, Issue 11, 14 March 2017, Pages 2608-2621
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Article
Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells

https://doi.org/10.1016/j.celrep.2017.02.056Get rights and content
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Highlights

  • Aging alters intestinal architecture and intestinal stem cell (ISC) function

  • ISC function is altered because of reduced canonical Wnt signaling upon aging

  • Canonical Wnts are reduced in ISCs, Paneth cells, and mesenchyme

  • Reactivating canonical Wnt signaling in aged ISCs restores function in organoids

Summary

Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay. Our data demonstrate a role for impaired Wnt signaling in physiological aging of ISCs and further identify potential therapeutic avenues to improve ISC regenerative potential upon aging.

Keywords

aging
regeneration
intestinal stem cells
Wnt signaling

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