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Those annoying gray hairs that tend to crop up with age really are signs of stress, according to a new study.
The research, published in the journal Nature, found that 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.
"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 study senior author Ya-Chieh Hsu from Harvard University in the US.
Because stress affects the whole body, researchers first had to narrow down which body system was responsible for connecting stress to hair colour.
The team first hypothesised 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. But once more, it was a dead end.
"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," Hsu added.
After systematically eliminating different possibilities, 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 colour the hair.
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.
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.
"We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells," said study researcher Isaac Chiu.
"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," Chiu added.