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Scientists Discover Link Between Nervous System And Pigment-Regenerating Stem Cells: Puzzle Solved: How Stress Causes Gray Hair.

CAMBRIDGE, Mass., January 22, 2020 -- Harvard University scientists have found evidence to support long-standing anecdotes that stress causes hair graying.

Researchers found that in mice, the type of nerve involved in the fight-or-flight response causes permanent damage to the pigment-regenerating stem cells in the hair follicle.

The findings advance knowledge of how stress impacts the body, and are a first step toward blocking its negative effects.

When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight.

In more recent history, the late Sen. John McCain experienced severe injuries as a prisoner during the Vietnam War--and lost color in his hair.

Now scientists here have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response and cause permanent damage to pigment-regenerating stem cells in hair follicles.

The study advances scientists' knowledge of how stress can impact the body.

"We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues," said senior author Ya-Chieh Hsu. "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 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, researchers turned to the hormone cortisol--a dead end.

"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.

After systematically eliminating different possibilities, researchers homed in on the sympathetic nerve system 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.

They found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively and convert into pigment-producing cells, prematurely depleting the reservoir.

"Once they're gone, you can't regenerate pigment anymore," Hsu said. "The damage is permanent."

The finding underscores the negative side effects of an otherwise protective evolutionary response, the researchers said.

To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed in on 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.

To go from the highest level to the smallest detail, scientists across a wide range of disciplines used different approaches to solve a very fundamental biological question.

Peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells.

With this study, researchers 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.

"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," Hsu said.

"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."

Citation: Bing Zhang et al., Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature, 2020; DOI: 10.1038/s41586-020-1935-3


Contact: Ya-Chieh Hsu,
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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Jan 27, 2020
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