History is replete with anecdotes, more and less verified, of individuals whose hair turned white or gray due to stress.

Marie Antoinette’s hair was said to have turned the color of snow overnight while she awaited the guillotine during the French Revolution. The late Sen. John McCain, a Navy pilot during the Vietnam War, suffered multiple serious injuries when his plane crashed in North Vietnam and during beatings while a prisoner of war — and lost color in his hair.

Now, for the first time, a group of Harvard researchers have discovered why that happens: Stress activates nerves that are part of the fight-or-flight response, which in turn causes permanent damage to pigment-regenerating stem cells in hair follicles. Their study on graying has just been published in Nature, and the results offer new insights into how stress can impact the body.

“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,” said senior author Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. “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.”

Because stress affects the whole body, researchers first had to narrow down which specific systems were involved. The team first hypothesized that stress causes an immune attack on pigment-producing cells. However, when mice lacking immune cells still showed hair graying, researchers turned to the hormone cortisol. Once again, they found a dead end.