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

    Chih Chiang Chen, Philip J. Murray, Ting Jiang, Maksim V. Plikus, Yun Ting Chang, Oscar K. Lee, Randall B. Widelitz, Cheng Ming Chuong
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    TLDR Aging mice have slower hair regeneration due to changes in signal balance, but the environment, not stem cell loss, controls this, suggesting treatments could focus on environmental factors.
    The study explored hair follicle regeneration in aging mice and the influence of extra-follicular modulators. It was discovered that hair regeneration slows down in mice over 18 months old due to increased levels of inhibitors like Bmp2, Dkk1, and Sfrp4, and decreased levels of activators such as follistatin. Transplanting aged mouse skin to young hosts showed that hair stem cells in aged skin could be reactivated, indicating that the macroenvironment significantly affects hair cycling. The study concluded that the balance of activator and inhibitor signals in the macroenvironment regulates hair regeneration, and that environmental factors rather than stem cell depletion are responsible for the altered hair regeneration patterns seen in aging. Mathematical modeling supported these findings, suggesting that treatments targeting the macroenvironment could mitigate aging-related changes in hair regeneration.
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