On the night before her execution, Marie Antoinette’s hair is said to have turned completely white. John McCain, after enduring terrible conditions as a prisoner of war at age 36 in Vietnam, emerged with white hair, too. Age-old wisdom posits that stress can fuel such a dramatic loss of hair color. Now, a study published in Nature suggests that the adage might be true—at least when it comes to mice.
In each follicle of human hair are melanocyte stem cells (MeSCs), which differentiate into specialized cells called melanocytes. These cells in turn dictate hair color by injecting pigment into the hair’s keratin. Over time, a person’s stores of MeSCs are slowly depleted. For Nature, Shayla A. Clark and Christopher D. Deppmann explain that with age, pigment disappears from hair follicles, and a person's hair gradually goes from "salt-and-pepper colored" to gray and then to white.
But scientists at Harvard University were interested in the processes that might fuel a more rapid loss of pigmentation. “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,” says senior author Ya-Chieh Hsu, a Harvard stem cell expert and regenerative biologist. “We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues.”
The first challenge that Hsu and her colleagues faced was figuring out what system could cause hair to go white due to stress. Initially, they hypothesized that one of two factors might be at play: Either stress led to an immune attack on pigment-producing cells, or cortisol—the primary stress hormone—was driving the change. But neither seemed to be the case. When the researchers removed adrenal glands from black-haired mice, rendering them unable to produce cortisol-like hormones, the fur of the unfortunate critters still turned gray after being exposed to stressful situations—like cage titling, isolation, damp bedding, rapid light and dark changes, and the injection of an analogue of capsaicin, the compound that gives chili peppers their heat. Mice lacking immune cells went gray, too.
Next, the researchers turned their attention to the sympathetic nervous system, responsible for a variety of functions including the fight-or-flight response. Sympathetic nerves extend into each of the skin’s hair follicles. Under stress, Hsu and her colleagues found, the sympathetic nervous system is active and produces the chemical norepinephrine, which in turn triggers melanocyte stem cells to go into overdrive, all of them converting to pigment-producing cells. Eventually, stores of MeSCs run out, depleting the follicle of its source of pigmentation.
“Once [the stem cells] gone, you can't regenerate pigment anymore. The damage is permanent."
Hsu was surprised by these findings; though it was previously known that the sympathetic nervous system is activated under stress, “you normally think about it as an emergency system, for fight-or-flight responses that are at the very least transient and reversible once the threat is gone,” she tells Time’s Alice Park. “But here, we found that the sympathetic nervous system can permanently deplete an entire stem cell population.”
Also surprising was just how quickly the sympathetic nervous system set to work; in many of the mice’s hair follicles, MeSCs were completely lost within five days. Knvul Sheikh of the New York Times reports that the researchers also found that human MeSCs behaved similarly in a petri dish, suggesting that our hair might react in the same way to stress.
While going gray might seem like more of a vanity issue than a health one, the new study underscores how stress may affect the human body in dramatic ways that medical professionals still do not entirely comprehend. “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 explains. "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.”
But, she adds, “We still have a lot to learn in this area.”