Just a quick look at Barack Obama in 2008 and Barack Obama in 2016 illustrates one of the not-so-silver linings of stress — it can make your hair turn gray. Obama isn't alone. From John McCain to Marie Antoinette — lots of people have reported hair color changes after periods of intense stress. But nailing down exactly why stress seeps the color out of hair has proved challenging — until now.
In a new study on mice with black coats, researchers discovered that the reason hair loses color as a result of stress may be down to the body's sympathetic nervous system. The sympathetic nervous system controls our body’s fight-or flight-response, triggering a chemical called norepinephrine to circulate throughout the body and making us alert and ready to meet a threat in our environment. But norepinephrine also sends certain cells — pigment-containing stem cells that live in hair follicles — into overdrive. These cells are what give hair its color — and norepinephrine kills them. As a result, with enough stress, hair can lose its pigment.
"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," Ya-Chieh Hsu, researcher at Harvard University and senior author of the study, said in a press release.
The change is irreversible, the study suggests. And the findings extend beyond people’s heads — they point out a dark side of fight-or-flight, a protective evolutionary mechanism.
"Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal's survival. But in this case, acute stress causes permanent depletion of stem cells," Bing Zhang, an author of the study and researcher at Harvard University, said.
The study was published Wednesday in the journal Nature.
Down the rabbit hole
Originally, the team thought the immune system might be attacking hair color cells. But after removing immune cells from mice, their coats still turned gray under stress.
Next, the researchers turned to the stress hormone, cortisol. In a second experiment, the team removed the mice’s adrenal glands, which produce cortisol-like hormones. But even without cortisol, the mice’s coats still went gray with stress.
After knocking out these possibilities, the researchers focused on the sympathetic nervous system. Stress triggers sympathetic nerves, which branch out into hair follicles, to produce norepinephrine. Nearby stem cells take up the chemical, a process that can have irreversible consequences.
Each hair follicle contains a trove of stem cells, which convert into pigment-producing cells and give hair strands their color. But norepinephrine causes the stem cells to over-activate, making them all convert into pigment-producing cells. This prematurely depletes the “reservoir” of stem cells. As a result, the next time the hair grows, there aren’t any stem cells to give hair its color.
As humans age, these pigment-producing cells gradually die anyway — that's why many elderly folks have gray, silver, or white hair. But this study suggests that stress speeds up the process, aging the body prematurely.
"After just a few days, all of the pigment-regenerating stem cells were lost,” Hsu said. “Once they're gone, you can't regenerate pigment anymore. The damage is permanent."
Stress out, stress in
The affects of stress on hair and skin may be visible to the human eye, but scientists are only just beginning to understand how stress affects the body — both on the outside and the inside.
"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," Hsu said.
More studies, in humans, are needed to understand how stress — from acute or chronic stressors — gives people a head of gray hair. Further investigation may also reveal just how far reaching stress's physiological effects go in the body, contributing to disease and threatening longevity.
"Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area."
Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)1,2, but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics3,4, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress- induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.