Hair Falling Out From Stress? Resting Stem Cells Point to WhyNews
The Problem: We’ve all heard of – or experienced – hair loss due to stress. But the reasons behind this phenomenon have been unexplored.
Why it Matters: This study pinpoints a way in which stress affects the body – specifically our hair – opening the door for better understanding of the broader effects of stress and how to mitigate them.
We’ve all felt the perils of stress, and while we know anecdotally how they affect our bodies, the exact mechanisms that drive these changes are unknown.
“My lab is interested in understanding how stress affects stem cell biology and tissue biology, spurred in part by the fact that everyone has a story to share about what happens to their skin and hair when they are stressed,” said Dr. Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard in a press release.
“I realized that as a skin stem cell biologist, I could not provide a satisfying answer regarding if stress indeed has an impact — and more importantly, if yes, what are the mechanisms,” she continued. “The skin offers a tractable and accessible system to study this important problem in depth, and in this work, we found that stress does actually delay stem cell activation and fundamentally changes how frequently hair follicle stem cells regenerate tissues.”
Stress Impacts the Routine of a Hair Follicle
Hair follicles cycle between periods of growth and rest: in growth phases, stem cells regenerate hair and well as the follicle itself to help hair grow. In rest phases, stem cells take a break, leaving follicles dormant and hair more likely to fall out. If stem cells stay dormant for too long, then hair can’t regenerate and hair loss accumulates.
To examine how stress impacts hair growth, the researchers subjected mice to different stressors such as tilted cages or flashing lights and examined stem cell behavior in hair follicles. Chronic stress caused the mice’s adrenal glands to produce a hormone called corticosterone – the equivalent in humans being cortisol, or the ‘stress hormone’. The team found that this stress hormone causes follicles to stay in an extended resting phase, essentially barring them from regenerating themselves, or hair.
“This result suggests that elevated stress hormones indeed have a negative effect on hair follicle stem cells,” Dr. Hsu said. “But the real surprise came when we took out the source of the stress hormones.”
Absent Adrenal Glands Spark Hair Growth
The scientists then removed the mice’s adrenal glands, the source of stress hormones, to see how absence of the hormone affects hair growth. Without stress hormones, the hair follicle stem cells’ resting phase to be significantly shortened, and the mice grew much more hair throughout their life, even as they aged.
“So even the baseline level of stress hormone that’s normally circulating in the body is an important regulator of the resting phase. Stress essentially just elevates this preexisting ‘adrenal gland-hair follicle axis,’ making it even more difficult for hair follicle stem cells to enter the growth phase to regenerate new hair follicles,” Dr. Hsu explained.
Tying Hormones to Hair Growth
The team then began exploring how exactly stress hormones interact with the hair follicle to impact hair growth.
“We first asked whether the stress hormone was regulating the stem cells directly and checked by taking out the receptor for corticosterone, but this turned out to be wrong. Instead, we found that the stress hormone actually acts on a cluster of dermal cells underneath the hair follicle, known as the dermal papilla,” said Sekyu Choi, PhD, the lead author of the study.
Dermal papilla typically help activate hair follicle stem cells, and the team found that corticosterone prevented dermal papilla cells from secreting Gas6, a molecule that aids in this process.
“Under both normal and stress conditions, adding Gas6 was sufficient to activate hair follicle stem cells that were in the resting phase and to promote hair growth,” Dr. Choi said. “In the future, the Gas6 pathway could be exploited for its potential in activating stem cells to promote hair growth. It will also be very interesting to explore if other stress-related tissue changes are related to the stress hormone’s impact on regulating Gas6.”
Understanding Stress in the Body
Last year, Dr. Hsu’s team found that stress can turn hair gray by depleting a group of stem cells responsible for giving hair its pigment. Her new study shows that hair loss due to stress is brought on by a completely different mechanism, but both are powerful demonstrations of the effects of stress on the body.
Dr. Hsu also stressed that her findings illuminate the interconnectedness of the body, and understanding issues that affect hair and skin likely involve examination beyond these tissues themselves.
“When looking for factors that control stem cell behaviors, normally we would look locally in the skin. While there are important local factors, our findings suggest that the major switch for hair follicle stem cell activity is actually far away in the adrenal gland and it works by changing the threshold required for stem cell activation,” Dr. Hsu said.
“You can have systemic control of stem cell behavior located in a different organ that plays a really important role, and we are learning more and more examples of these ‘cross-organ interactions.’ Tissue biology is interconnected with body physiology. We still have so much to learn in this area, but we are constantly reminded by our findings that in order to understand stem cells in the skin, we often need to think beyond the skin.”
Photo credit: Jon Chase/Harvard Staff Photographer
Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence.
Sekyu Choi, Bing Zhang, Sai Ma, Meryem Gonzalez-Celeiro, Daniel Stein, Xin Jin, Seung Tea Kim, Yuan-Lin Kang, Antoine Besnard, Amelie Rezza, Laura Grisanti, Jason D. Buenrostro, Michael Rendl, Matthias Nahrendorf, Amar Sahay, Ya-Chieh Hsu. Nature. 2021. DOI: 10.1038/s41586-021-03417-2
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