Hair loss concept of close up hairbrush and fallen hair.

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

According to a mouse study published in the journal Nature, a major stress hormone induces follicle stem cells into prolonged rest, without rejuvenating the follicle or hair follicles. The researchers identified the specific cell type and molecule responsible for transmitting stress signals to stem cells, and showed that this approach may be aimed at restoring hair growth.

My lab is interested in understanding how it affects my cell biology and tissue biology, as everyone has a history of what happens to their skin and hair during stress. As a skin stem cell biologist, I realized that if stress really affects — I can’t answer — and most importantly, what are the strategies? Professor of Stem Cell and Regeneration Biology in Harvard and senior author of the study. The skin provides an invasive and accessible system for in-depth study of this important problem, and in this process we find that stress actually slows down stem cell activation and fundamentally alters how hair follicle stem cells regenerate tissue.

The hair follicle is one of the few mammals that can undergo renewal cycles throughout its life, and it is an example of our basic understanding of mammalian cell biology. The hair follicles rotate naturally between growth and rest, a process in which hair follicle cells are burned. During the growing season, follicle stem cells move to regenerate the follicle and hair, and hair grows longer every day. During the rest, the stem cells are fast and the hairs flow easily. Hair loss can occur if the hair follicles fall out and the stem cells do not regenerate new tissue.

Under the mouse’s hair, dermal papillae (green) produce 6 molecules of gas that stimulate hair follicle stem cells. Credit-Hsu Laboratory, Harvard University

The researchers studied the model of chronic stress and found that hair follicle stem cells remained at rest for a long time without regenerating tissue. In adrenal glands, corticosteroid, a major stress hormone, is regulated by chronic stress; Mice giving corticosteroids redistributed stress to stem cells. In humans, the hormone cortisol, which is regulated by stress, is often called the “stress hormone.”

“As a result, high levels of stress hormones actually affect the hair follicle stem cells,” he said. But when we released the source of the stress hormones, a real surprise occurred.

Under normal circumstances, the growth of the hair follicles decreases over time – the longer the animal grows, the longer the rest period. But as the researchers removed the stress hormones, the cells’ rest period became too short, and the rats entered the developmental stage to regenerate hair follicles throughout their lives.

Therefore, even the normal level of stress hormones in the body is a necessary regulator of rest. Stress mainly increases the existing adrenal gland follicle axis, making it more difficult for hair follicle cells to re-enter the developmental stage. ”

After establishing a link between stress hormone and hair follicle stem cell activity, the researchers looked for a biological mechanism based on the relationship.

“At first we asked if the stress hormone directly controls the cells and it was tested by releasing a corticosterone receptor, but this was a mistake. Instead, we have come to know that the stress hormone actually works on the skin cells under the hair follicles, ”says the study’s lead author, Seku Choi.

Dermal papilla is known to be important in stimulating hair follicle stem cells, but none of the previously secreted dermal papillas have been altered by stress hormone levels. Instead, the stress hormone inhibits the secretion of the molecular gas 6, the dermal papilla.

“In normal and stressful situations, adding 6 gas was enough to stimulate the hair follicle stem cells during rest and promote hair growth,” Choi said. “The future 6 gas pathways can be used to stimulate hair growth by stimulating stem cells. If other stress-related tissue changes are related to the regulation of stress hormone gas 6, it will be interesting to explore.

These early discoveries in mice need to be studied further before they can be safely applied to humans. The Harvard Technology Development Office is exploring intellectual property in connection with this work and exploring opportunities for future growth and future business collaboration.

Last year, the Hsu group discovered how stress affects other hair cells. The researchers said that stress stimulates the sympathetic nervous system and depletes melanocyte stem cells, leading to premature hair loss. In the new study, the combined findings of the two findings may have different effects on both hair follicle cells and melanocytes. Stress depletes melanocytes stem cells directly through neurological symptoms, and stress directly inhibits the growth of hair follicle cells by stress hormones found in the adrenal gland. Since hair follicle cells are not depleted, it may be possible to reactivate stem cells under the stress of mechanisms such as gas 6.

In addition to the use of natural gas to promote hair growth, the results of the study have far-reaching implications for cell biology.

“When we look for stem cell controls, we usually look at the skin. Despite important environmental factors, our findings suggest that the main modifier for hair follicle stem cell activity is actually the remotest point in the adrenal gland and changes the threshold needed for cell activation. ”

“You may have systematic control of stem cell behavior in a particular organ that plays a very important role, and we are learning more and more examples of these ‘organ interactions’. Tissue biology is related to the physiology of the body. We still have a lot to learn in this area, but we always remember from our findings that in order to understand the cells in our skin, we often have to think beyond the skin.

This work is partly funded by the New York Tree Cell Foundation, the Smith Family Foundation Audit Award, Pew Charity Trust, Harvard Stem Cell Institute, Harvard HMS Dean Award, American Cancer Society, James and Aurry Foster MH Research Scholar Award, NARSAD Youth MGH ECOR Fund, New York State Department of Health, and National Health Institutions.