Going Gray? Stress — and Depleted Stem Cells — Are the Likely Culprits

The Context: We’ve all heard that stress can turn your hair gray. But there hasn’t been much scientific evidence that this is true — and if so, how it happens.

The Study: It turns out that stress can, in fact, turn hair gray. Stress activates your sympathetic nervous system – the system that controls your ‘fight or flight’ response – depleting a group of stem cells responsible for giving hair its pigment and resulting in gray hair, finds a new study in Nature by NYSCF – Robertson Stem Cell Investigator Dr. Ya-Chieh Hsu of Harvard University.

The Importance: This study illuminates a previously unknown link between stress and the function of an important stem cell population, opening the door for a better understanding of the physiological effects of stress and how they can be mitigated.


“I’m going to go gray over this.”

When someone says this, we all know what they’re talking about: stress.

“Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair — the only tissues we can see from the outside,” NYSCF – Robertson Stem Cell Investigator Ya-Chieh Hsu, PhD, told The Harvard Gazette. “We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with — and besides, we were genuinely curious to see if stress indeed leads to hair graying.”

Dr. Hsu’s new study in Nature proves that stress does in fact lead to graying locks, and it does so by acting on the stem cells that spark pigment production.

Stressed Stem Cells Lead to Silver Strands

Dr. Hsu’s first thought was that stress-induced graying may be due to an immune attack on stem cells that give rise to pigment producing cells. But mice with disabled immune systems still went gray under stress, so that couldn’t be it.

Then, she thought the gray hair might be the work of cortisol, the stress-induced hormone. But mice without the cortisol-producing adrenal glands also went gray when stressed out. Another dead end.

That brought Dr. Hsu to the sympathetic nervous system. It’s the system that kicks in when we are in an emergency situation, prompting us to ‘fight or flee.’ Through an elegant series of experiments, the researchers found that activation of the sympathetic nervous system directly leads to permanent depletion of pigment-regenerating stem cells in the hair follicle, in turn causing growth of gray hair.

‘Fight or Flight’ Acts on the Hair Follicle

When you’re stressed, even outside of an emergency situation, your sympathetic nervous system is still active. Your body will start to produce a chemical called norepinephrine, which signals to pigment-regenerating stem cells in the hair follicle to activate and migrate out of the follicle. This permanent loss of melanocyte stem cells leaves the follicle without pigment to give hair its color, causing new hairs to come in gray.

“When we started to study this, I expected that stress was bad for the body — but the detrimental impact of stress that we discovered was beyond what I imagined,” remarked Dr. Hsu. “After just a few days, all of the pigment-regenerating stem cells were lost. Once they’re gone, you can’t regenerate pigments anymore. The damage is permanent.”

What’s Next?

This study illuminates an unknown link between stress and stem cells, opening the door for broader research on the effects of stress and how they can be prevented or modified.

“By understanding precisely how stress affects stem cells that regenerate pigment, we’ve laid the groundwork for understanding how stress affects other tissues and organs in the body,” said Dr. Hsu. “Understanding how our tissues change under stress is the first critical step toward eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area.”

Photo credit: Jon Chase/Harvard Staff Photographer

Journal Article:

Hyperactivation of Sympathetic Nerves Drives Depletion of Melanocyte Stem Cells
Bing Zhang, Sai Ma, Inbal Rachmin, Megan He, Pankaj Baral, Sekyu Choi, William A. Gonçalves, Yulia Shwartz, Eva M. Fast, Yiqun Su, Leonard I. Zon, Aviv Regev, Jason D. Buenrostro, Thiago M. Cunha, Isaac M. Chiu, David E. Fisher & Ya-Chieh Hsu. Nature. 2020. DOI: https://doi.org/10.1038/s41586-020-1935-3

Read more in:

The New York Times 

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Time

Diseases & Conditions:

Stem Cell Biology