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Genes & Dev. 26 (19): 2144-2153

Copyright © 2012 by Cold Spring Harbor Laboratory Press.

Age-associated inflammation inhibits epidermal stem cell function

Jason Doles1,2, Mekayla Storer1,2, Luca Cozzuto1,2, Guglielmo Roma1,2,3,, and William M. Keyes1,2,4

1 Centre for Genomic Regulation (CRG), Barcelona 08003, Spain;
2 Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain

Abstract: Altered stem cell homeostasis is linked to organismal aging. However, the mechanisms involved remain poorly understood. Here we report novel alterations in hair follicle stem cells during skin aging, including increased numbers, decreased function, and an inability to tolerate stress. Performing high-throughput RNA sequencing on aging stem cells, cytokine arrays, and functional assays, we identify an age-associated imbalance in epidermal Jak–Stat signaling that inhibits stem cell function. Collectively, this study reveals a role for the aging epidermis in the disruption of cytokine and stem cell homeostasis, suggesting that stem cell decline during aging may be part of broader tumor-suppressive mechanisms.

Key Words: stem cells • aging • epidermis • Jak–Stat

Received for publication March 16, 2012. Accepted for publication August 10, 2012.

3 Present address: Novartis Institute for Biomedical Research, WSJ-Fabrikstrasse 22.4.025.10, CH-4002 Basel, Switzerland.

4 Corresponding author

E-mail bill.keyes{at}crg.eu

Supplemental material is available for this article.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.192294.112.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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R. Tokarsky-Amiel, N. Azazmeh, A. Helman, Y. Stein, A. Hassan, A. Maly, and I. Ben-Porath (2013)
Cancer Res. 73, 2829-2839
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