Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells.

Nalapareddy K, Nattamai KJ, Kumar RS, Karns R, Wikenheiser-Brokamp KA, Sampson LL, Mahe MM, Sundaram N, Yacyshyn MB, Yacyshyn B, Helmrath MA, Zheng Y, Geiger H
Cell Rep. 2017 18 (11): 2608-2621

PMID: 28297666 · PMCID: PMC5987258 · DOI:10.1016/j.celrep.2017.02.056

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.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (13)

Animals Biomarkers Cell Count Cell Proliferation Cellular Senescence Female Intestine, Small Mice Organoids Regeneration Stem Cell Niche Stem Cells Wnt Signaling Pathway

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