Have you ever wondered if the notion that extreme distress causes premature gray hair is just an old wives' tale or if there might be some truth to it? Over the centuries, there's been lots of speculation, but very little scientific research to verify—or debunk—the idea that stress causes gray hair.
Now, a team of researchers from Harvard University and the Center for Research on Inflammatory Diseases (CRID) in São Paolo have identified a link between hyperactivation of the sympathetic nervous system, a surge in norepinephrine, and the depletion of specific stem cells that regenerate pigment in the hair follicles of mice. This chain reaction turns hair white. These findings (Zhang et al., 2020) were published on January 22 in the journal Nature.
Typically, men and women start to experience some gray hairs in their thirties and will likely have a significant amount of gray hair by their fifties. Do you know someone who claims that severe stress or trauma turned his or her hair prematurely gray? Has this happened to you?
The most notorious case of supposedly stress-related loss of hair pigmentation (i.e., achromotrichia) is probably Marie Antoinette (1755-1793).
As the legend goes, during the French Revolution, Antoinette went from being brash and purportedly saying "Let them eat cake!" to being scared to death when she was found guilty of treason and sentenced to the guillotine in 1793.
At the time, there were rumors and sensationalized reports that her hair turned white overnight. Antoinette's First Lady of the Bedchamber, Henriette Campman, wrote in her memoirs, "En une seule nuit ils étaient devenus blancs comme ceux d'une femme de soixante-dix ans." (Translation: "In a single night, [her hair] had turned as white as that of a 70-year-old woman.")
Despite the hyperbole surrounding Marie Antoinette's hair turning white overnight, we now have some scientific evidence that there may be some truth to stories of acute distress causing someone's hair to lose pigment.
"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," senior author Ya-Chieh Hsu of Harvard University said in a news release. "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."
Elaborate sympathetic innervation (magenta) around melanocyte stem cells (yellow). Acute stress induces hyperactivation of the sympathetic nervous system to release a large amount of the neurotransmitter norepinephrine. Norepinephrine drives the rapid depletion of melanocyte stem cells and hair greying.Source: Hsu Laboratory, Harvard University
"For the longest time it's been said that stress makes the hair turn white, but until now there was no scientific basis for this belief. Our study proved that the phenomenon does indeed occur, and we identified the mechanisms involved. In addition, we discovered a way of interrupting the process of hair color loss due to stress," co-author Thiago Mattar Cunha of CRID added.
Interestingly, when the researchers set out to discover why acute stress can cause gray hair, they expected cortisol (i.e., the "stress hormone") to be the main culprit. "Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role," Hsu said. "But surprisingly, when we removed the adrenal gland from the mice so that they couldn't produce cortisol-like hormones, their hair still turned gray under stress."
After they realized that cortisol wasn't a prime driver of hair turning white, the researchers broadened their focus to the entire sympathetic nervous system (SNS), which drives the fight-or-flight response in humans and mice.
The researchers, who used a laboratory strain of dark-furred mice, observed that SNS nerves branch out and touch every hair follicle. When a mouse experienced acute pain-induced stress in the lab, it triggered a fight-or-flight stress response in the autonomic nervous system that caused norepinephrine levels to surge, which wiped out the pigment-regeneration capability of stem cells in the hair follicle. "After just a few days, all of the pigment-regenerating stem cells were lost. Once they're gone, you can't regenerate pigment anymore. The damage is permanent," Hsu noted.
"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," lead author Bing Zhang, who is a postdoctoral fellow in the Hsu Lab at Harvard, added.
Another takeaway from this research is that the "transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair graying." Notably, the researchers found that treating stressed-out mice with an anti-hypertensive that inhibited the neurotransmission of SNS nerve fibers to the hair follicle blocked fur-color loss.
Beyond stress-related gray hairs, this research has broader implications of how acute stress can cause the permanent loss of somatic stem cells and how the overall physiological state of an organism influences the maintenance of these stem cells. This research could pave the way for other studies that identify specific ways to combat hyperactive fight-or-flight stress responses.
"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 concluded. "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."
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. "Hyperactivation of Sympathetic Nerves Drives Depletion of Melanocyte Stem Cells." Nature (First published: January 22, 2020) DOI: 10.1038/s41586-020-1935-3