Mystery of how stress turns hair gray finally solved by Harvard team

Back in 2009, a New York Times article appeared with the headline, “After 44 days in the White House, Obama’s hair is grayer.” The article referred to a common trend of presidents’ hair turning dramatically gray during their terms in the Whitehouse.

This idea of stress turning hair gray has pervaded popular culture for centuries. It’s often referred to as Marie Antoinette syndrome, in reference to an oft-told, but most likely apocryphal, story of the ill-fated French queen’s hair turning white overnight after being captured during the revolution.

While the idea of one’s hair turning white in an instant after a sudden fright is an amusing cartoonish fiction, there is a solid body of anecdotal evidence describing instances where hair rapidly turns white after months, or even weeks, of stress or trauma.

“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,” explains senior author on the new study, Ya-Chieh Hsu. “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.”

Before this new research, not only was it a mystery as to how hair turns gray in times of stress, many scientists even questioned whether stress could actually directly cause hair to turn gray. It was generally thought that times of stress simply accelerated the aging process, and it was this mechanism that rapidly turned hair gray.

In the early stages of this new Harvard research the team certainly may have suspected the common consensus to be correct, but each initial hypothesis quickly led the researchers to dead ends. Was stress causing immune cells to eliminate those pigment-producing cells in hair follicles? Nope, that wasn’t it. How about the well-studied stress hormone cortisol? Surely that must be playing a role in hair graying?

“Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role,” says Hsu. “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.”

The initial breakthrough arrived when the researchers discovered that when mice are stressed, their hair begins to grow gray due to a depletion in specific stem cells that reside in the base of hair follicles. These stem cells turn into pigment-producing cells as hair grows but in times of great stress these stem cells are overactivated. This depletes the follicle’s reservoir of pigment-producing stem cells, causing the subsequent hair growth to become 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,” says 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.”

But this discovery didn’t explain exactly how stress was activating these stem cells. It was soon discovered that norepinephrine seemed to be triggering the excessive stem cell depletion. However, removing the animal’s primary source of norepinephrine, the adrenal gland, did not stop the stress-induced graying.

The solution to this mystery lay in the body’s other main source of norepinephrine, the sympathetic nervous system (SNS), commonly known as our fight-or-flight system.

The researchers discovered that acute stress triggers a release of norepinephrine from SNS neurons. This neurotransmitter subsequently activates the mass migration of stem cells from the base of a hair follicle, and it is this process that directly connects stress with hair graying.

“Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal’s survival,” explains Bing Zhang, lead author on the new study. “But in this case, acute stress causes permanent depletion of stem cells.”

It is unclear at this stage whether the mechanism the Harvard team discovered is part of the natural process of age-related hair graying. Is this stress-induced graying simply an accelerated version of what naturally happens to many people over several decades?

Shayla Clark and Christopher Deppman, two neuroscientists from the University of Virginia, penned an editorial in the journal Nature, accompanying the publication of the new study. Calling the Harvard study “fascinating,” Clark and Deppman intriguingly hypothesize what particular evolutionary function this kind of stress-induced graying could serve.

“Because gray hair is most often linked to age, it could be associated with experience, leadership and trust,” the duo suggest. “For example, adult male silverback mountain gorillas (Gorilla beringei beringei), which get grey hair on their backs after reaching full maturity, can go on to lead a gorilla troop. Perhaps an animal that has endured enough stress to ‘earn’ grey hair has a higher place in the social order than would ordinarily be conferred by that individual’s age.”

Separate from these academic evolutionary considerations, the new research shines a compelling light on how acute stress can play a direct role on the activity of stem cells. Discovering this novel mechanism, of course, paves the way for new methods that could prevent hair graying, but even more importantly, the study opens the door to new ways to examine the effects of stress on other organs in the body.

“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,” concludes 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.”

The new research was published in the journal Nature.

Source: Harvard Gazette