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Researchers Discover How Chronic Stress Leads to Hair Loss – Harvard Gazette

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Researchers at Harvard University have identified the biological mechanisms by which chronic stress damages hair follicle stem cells and confirm long-standing observations that stress can lead to hair loss.

In a mouse study published in a journal NatureResearchers have found that major stress hormones put hair follicle stem cells in a long telogen phase without regenerating hair follicles or hair. Researchers have identified specific cell types and molecules that are responsible for relaying stress signals to stem cells, and have shown that this pathway can potentially be targeted to restore hair growth. It was.

“My lab is interested in understanding how stress affects stem cell biology and tissue biology. This is what happens to the skin and hair when stressed. Partly spurred by the fact that there is a story that everyone can share about what happens. Alvin and Esta star associate Ya-Chieh Hsu, as a skin stem cell biologist, does stress really affect? Please, and more importantly, I realized that I couldn’t provide a satisfactory answer about the mechanism if it had an effect. He is a professor of stem cell and regenerative biology at Harvard University and a senior author of the study. It provides an easy-to-use and accessible system for studying this important issue in detail. In this study, stress actually delays stem cell activation and fundamentally how often hair follicle stem cells regenerate tissue. I found that it would change. “

Hair follicles are one of the few mammalian tissues that can regenerate throughout life and are a paradigm that conveys much of the basic understanding of mammalian stem cell biology. Hair follicles naturally circulate between growth and rest. This is a process facilitated by hair follicle stem cells. During anagen, hair follicle stem cells are activated to regenerate hair follicles and hair, and the hair follicles grow longer every day. During telogen, stem cells become quiescent, making it easier for hair to fall out. Hair loss can occur if hair loss occurs and the stem cells remain stationary without regenerating new tissue.

Mouse hair follicles.
Under the hair follicles of mice, papillary dermal cells (green) produce Gas6 molecules, which activate hair follicle stem cells.Credit: Harvard Sue Institute

Researchers studied a mouse model of chronic stress and found that hair follicle stem cells remained in telogen for a very long time without tissue regeneration. Corticosterone, the major stress hormone produced by the adrenal glands, has been upregulated by chronic stress. When mice were given corticosterone, the stress effect on stem cells was reproduced. The human equivalent hormone is cortisol, which is also upregulated under stress and is often referred to as the “stress hormone”.

“This result suggests that elevated stress hormones actually have a negative effect on hair follicle stem cells,” Sue said. “But when I removed the source of stress hormones, I was really surprised.”

Under normal conditions, hair follicle regeneration slows down over time. As the animal ages, the telogen period becomes longer. However, when researchers removed stress hormones, the telogen phase of stem cells became very short, and mice constantly entered a growth phase to regenerate hair follicles throughout their lives, even in old age.

“Therefore, even baseline levels of stress hormones that normally circulate in the body are important regulators of telogen. Stress essentially only raises this existing” adrenal-follicle axis. ” , Making it even more difficult for hair follicle stem cells to enter the telogen phase and regenerate new hair follicles, “says Sue.

After establishing a link between stress hormones and hair follicle stem cell activity, researchers sought out the underlying biological mechanisms of that link.

“We first asked if stress hormones regulate stem cells directly and then took out and examined the corticosterone receptors, which turned out to be wrong. Instead, stress hormones actually did. We have discovered that it acts on a cluster of dermal cells known as the dermal papilla under the hair follicle, “said Choi Se-hisa, the lead author of the study.

The papillary line is known to be important for activating hair follicle stem cells, but when stress hormone levels change, all previously identified factors secreted by the papillary line change. did not. Rather, stress hormones prevented dermal papilla cells from secreting Gas6. Gas6 is a molecule that researchers have shown to be able to activate hair follicle stem cells.

“In both normal and stressful conditions, the addition of Gas6 was sufficient to activate telogen hair follicle stem cells and promote hair growth,” Choi said. “In the future, the Gas6 pathway may be utilized because it may activate stem cells and promote hair growth. Other stress-related tissue changes are stress hormones for the regulation of Gas6. It would also be very interesting to investigate if it is related to the effects of. “

These first findings in mice need further study before they can be safely applied to humans.Harvard Technology Development Bureau We are looking for opportunities to collaborate on the protection of the intellectual property associated with this work and its further development and final commercialization.

Last year, Sue’s group discovered how stress affects another type of stem cell in the hair follicle, the melanocyte stem cell that regenerates hair pigments. Researchers have found that stress activates the sympathetic nervous system and depletes melanocyte stem cells. Leads to young gray hair.. A new study, together, shows that stress has a detrimental effect on both hair follicle stem cells and melanocyte stem cells, but with different mechanisms. Stress depletes melanocyte stem cells directly via nerve-derived signals, but stress prevents hair follicle stem cells from indirectly forming new hair through the effects of adrenal-derived stress hormones on the niche. I will. Since hair follicle stem cells are not depleted, they may be able to reactivate stem cells under stress by mechanisms such as the Gas6 pathway.

Beyond the potential application of the Gas6 pathway in promoting hair growth, the results of the study have broader implications for stem cell biology.

“When looking for factors that control stem cell behavior, we usually look at the skin locally. There are important local factors, but our finding is that the major switch in hair follicle stem cell activity is actually Is far away in the adrenal glands, suggesting that it works by changing the threshold required for stem cell activation, “Sue said.

“We can systemically control the behavior of stem cells in other organs that play a very important role. We are learning more and more examples of these” organ-to-organ interactions. ” Tissue biology correlates with the physiology of the body. There’s still a lot to learn in this area, but we’re always aware of the discovery that we need to think beyond the skin to understand skin stem cells. “

This work is partly by the New York Stem Cell Foundation, Smith Family Foundation Odyssey Awards, Petitable Trust, Harvard Stem Cell Institute, Harvard HMS Dean Awards, American Cancer Society, James and Audrey Foster MGH Research Scholar Awards, NARSAD Young Investigator. Supported. Awards, MGH ECOR Foundation, New York State Department of Health, and National Institutes of Health.

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