Ian Sample, The Guardian, Jan 22, 2020
Lord Byron put it down to sudden fears, which took their toll on men at night. For Wordsworth it was shocks of passion that swiftly turned hair white.
But while hair cannot lose its colour in an instant - at least not without help from a bottle of bleach - scientists at Harvard University have shown how stress can, over time, speed up the greying process.
Ya-Chieh Hsu, a stem cell biologist, found that stress causes nerves involved in the fight-or-flight response to pump out a hormone which wipes out the stem cells used to make hair pigments.
Because stress can be considered a form of accelerated ageing, the discovery has raised hopes for treatments that can slow down or even halt normal age-related greying. More importantly, it could shed light on how ageing depletes stem cells throughout the body, and perhaps point the way to general anti-ageing therapies.
Prof Christopher Deppmann, a biologist at the University of Virginia who was not involved in the work, said he believed it had “profound implications” for how scientists think about stem cell biology, stress biology and potentially the ageing process.
“Like any good study, it opens up at least as many questions as it answers, but it may represent an important stepping stone toward rationalising and developing pharmaceutical fountains of youth,” he said.
The Harvard team made their discovery through a series of experiments that measured the effect of stress on the hair colour of mice. The animals were stressed over several days by being restrained for four hours a day, Monday to Friday, or through combinations of damp bedding, rapid changes to lighting and having their cages tilted.
At first, the scientists suspected that stress triggered an immune attack on hair pigment-making cells, but ruled that out when they found that mice without immune cells still turned grey after episodes of stress. Next they considered cortisol, a hormone that rises in response to stress. This turned out to be another dead end: mice with no cortisol still developed grey hair.
The researchers eventually found the culprit in a set of nerves that make up the sympathetic nervous system. The nerves, which prepare the body for action as part of the fight-or-flight response, reach into hair follicles in the skin, and it is here that they do their damage.
Hair follicles contain a bulge that is home to a pool of stem cells. When a new hair is made, some of these stem cells turn into pigment-making ones called called melanocytes. A hair’s colour depends on the mix of light-absorbing melanin compounds that the melanocytes churn out.
Tests showed that stress causes the sympathetic nervous system to pump a hormone called noradrenaline, or norepinephrine, into the hair follicle bulge. The sudden inrush of noradrenalin has an extraordinary effect. The hormone converts huge numbers of stem cells into melanocytes, but no sooner are they made than they begin to drift away from the follicle and break down. The next time the follicle tries to make a hair, there are few or no stem cells left to generate fresh pigment-producing cells.
“Stress, through activation of the sympathetic nervous system, drives the loss of these melanocyte stem cells, the stem cells that are important in regenerating the pigment for the hair,” Hsusaid. “And once the reservoir has been depleted, that’s it.” The work is published in Nature.
Hsu suspects that a similar mechanism is responsible for age-related greying. “There are definitely shared responses between how the melanocyte stem cells respond to stress and how they respond to ageing,” she said. “You essentially lose the stem cell pool in ageing as well.”
It could take years of hard work to develop a safe and effective treatment to stop greying hair, Hsu said. What is more exciting, she believes, is that the work paves the way for understanding how the loss of stem cells throughout the body contribute to ageing.
“This is certainly one implication that I’m particularly excited about,” said Deppmann. “There has already been evidence that stress and the fight-or-flight response depresses stem cells that are important for immunity. This may be the reason we often get sick after prolonged periods of stress.
“I believe that we have only scratched the surface of whether and how stress and fight-or-flight mechanisms deplete other stem cell populations. Whether or not this is the cause of premature ageing remains to be determined, but I wouldn’t bet against it.”
It is unclear whether stress-related greying came about by providing an evolutionary advantage to ancient beasts, among them human ancestors. “Because grey hair is most often linked to age, it could be associated with experience, leadership and trust,” Deppmann writes in an accompanying article in Nature. “Perhaps an animal that has endured enough stress to ‘earn’ grey hair has a higher place in the social order than would ordinarily be conferred by that individual’s age.”
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