Regenerative Hair Waves in Aging Mice and Extra-Follicular Modulators Follistatin, Dkk1 and Sfrp4

Chih-Chiang Chen, Philip J. Murray, Ting Xin Jiang, Maksim V. Plikus, Yun-Ting Chang, Oscar K. Lee, Randall B. Widelitz, Cheng Ming Chuong (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)


Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging associated alopecia. Recently we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3?mm range of the interface, suggesting that changes are due to extra-cellular factors. Therefore, hair stem cells in aged skin can be re-activated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator which is highly expressed in late telogen and early anagen. Indeed follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the inter-organ macro-environment can regulate the aging process by integrating both "activator" and "inhibitor" signals.Journal of Investigative Dermatology accepted article preview online, 11 March 2014; doi:10.1038/jid.2014.139.
Original languageEnglish
Pages (from-to)2086-2096
Number of pages11
JournalJournal of Investigative Dermatology
Issue number8
Early online date17 Apr 2014
Publication statusPublished - Aug 2014


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