It is not uncommon to hear people say that stress causes one's hair to gray. Many famous American Presidents such as George W. Bush and Barrack Obama grayed drastically by the end of their taxing presidencies. Yet, the exact reason behind the process has eluded scientists... Until now.

Researchers from Harvard University have finally uncovered the precise mechanism that causes graying using mice. Stress triggers nerves that are closely involved in the fight-or-flight response. This, in turn, causes irreversible damage to pigment-regenerating stem cells that are found in the hair follicles.

"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," said Chieh Hsu, senior author of the study, in a statement.

Gray Hair
Representational Picture Pixabay

Zeroing in on the real culprit

Stress affects the entire body. Therefore, the researchers had to first ascertain which system of the body was responsible for linking hair colour to stress. The first hypothesises that was formulated was that stress leads to an immune attack against pigment-producing cells. However, the scientists found that in spite of lacking immune cells, some mice continued to exhibit graying of hair. This prompted the researchers to assess the hormone cortisol—which also did not prove to be the real culprit.

Citing the increase in the levels of cortisol as a response to stress, the team assumed that hormone played a role in the graying process—only to learn that it did not. "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," Hsu said.

The systematic elimination of possible causes

Following the striking down of immune response and cortisol levels from a list of possible causes, the researchers began systematically eliminating the various possibilities. Finally, they set their sights on the sympathetic nerve system, which is attributed to controlling the body's fight-or-flight response.

Gray Hair
Representational Picture Wikimedia Commons

Sympathetic nerves branch into every hair follicle on the skin. What the authors discovered was that stress promotes the release of the chemical norepinephrine by these nerves. The released chemical is absorbed by the pigment-regenerating stem cells that are situated nearby.

Irreversible damage

Specific stem cells within the hair follicle act as a reservoir of pigment-generating cells. During the regeneration of hair, some of the stem cells are converted into pigment-producing cells that give hair its color.

The team found that the norepinephrine produced by the sympathetic nerves causes uncontrolled activation of the stem cells. All the stem cells now turn into pigment-producing cells, which in turn lead to the premature depletion of the reservoir.

"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," said Bing Zhang, lead author of the study. Therefore, the study highlights the damaging side effects of a generally beneficial evolutionary response that is often considered vital for survival.

Barrack Obama
President Obama's hair famously grayed during the course of his presidency Wikimedia Commons

Making the connection between graying and stress

In order to make the connection between stress and graying, the researchers began with a complete-body response and gradually focussed on individual organ systems, cell-to-cell interactions, and finally, down to molecular dynamics. A range of research tools was employed for this process, including techniques to manipulate cell receptors, nerves and organs.

For the intrinsic study that focussed on various macro and micromechanisms of the body, the researchers collaborated with scientists across various disciplines. One such collaborator was Isaac Chiu, assistant professor of immunology at Harvard Medical School.

Pointing out that the current study learned beyond the various known capacities of neurons, Chiu said, "With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying."

Insight into the broad-ranging effects of stress

The researchers say that these findings may further the understanding of broad-ranging effects of stress on various types of tissues and organs. This knowledge will provide a new foundation to study and develop ways to block or modify the effects of stress.

"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," concluded Hsu.