When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight.
In more recent history, John McCain experienced severe injuries as a prisoner of war during the Vietnam War—and lost color in his hair.
For a long time, anecdotes have connected stressful experiences with the phenomenon of hair graying.
Now, for the first time, Harvard University scientists have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response, which in turn cause permanent damage to pigment-regenerating stem cells in hair follicles.
The finding advances scientists’ knowledge of how stress can impact the body.
In the study, the team wanted to understand if the connection between stress and grey hair is true, and if so, how stress leads to changes in diverse tissues.
Because stress affects the whole body, the researchers first had to narrow down which body system was responsible for connecting stress to hair color.
The team first hypothesized that stress causes an immune attack on pigment-producing cells.
However, when mice lacking immune cells still showed hair graying.
After systematically eliminating different possibilities, the researchers honed in on the sympathetic nerve system, which is responsible for the body’s fight-or-flight response.
Sympathetic nerves branch out into each hair follicle on the skin.
The researchers found that stress causes these nerves to release the chemical norepinephrine, which gets taken up by nearby pigment-regenerating stem cells.
In the hair follicle, certain stem cells act as a reservoir of pigment-producing cells. When hair regenerates, some of the stem cells convert into pigment-producing cells that color the hair.
The researchers found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively. The stem cells all convert into pigment-producing cells, prematurely depleting the reservoir.
The finding underscores the negative side effects of an otherwise protective evolutionary response.
To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed into individual organ systems, cell-to-cell interaction and, eventually, all the way down to molecular dynamics.
The process required a variety of research tools along the way, including methods to manipulate organs, nerves, and cell receptors.
The team says with this study, they 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.
The findings can help illuminate the broader effects of stress on various organs and tissues.
This understanding will pave the way for new studies that seek to modify or block the damaging effects of stress.
One author of the study is Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard.
The study is published in Nature.