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How does stress cause the premature graying of hair?

Written by Caitlin Killen

Scientists have demonstrated that there is some truth behind long-touted anecdotes that stress can cause untimely graying of hair.

A multi-institution, collaborative study, led by researchers at Harvard University (MA, USA), has discovered the mechanism by which stress plays a role in the premature graying of hair.

It has long been hypothesized that stress causes graying of hair, with many stories told about famous figures and their gray hair – Marie Antoinette supposedly went gray overnight prior to her execution.

“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,” commented senior author Ya-Chieh Hsu (Harvard University). “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.”

To investigate the mystery, the researchers had to ascertain the mechanism for the graying of hair. The team first hypothesized that the destruction of pigment-producing cells was immune-mediated; however, immunodeficient mice still presented with graying hair when exposed to stress.

Next, the team changed its focus to cortisol, a hormone in the body that is elevated during times of stress. Adrenal glands were removed from mice to inhibit the production of cortisol-like hormones. Despite this, gray hair was still observed under stress-inducing conditions.

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By systematically eliminating alternate options utilizing a combination of denervation, chemogenetics, cell ablation and the knockout of adrenergic receptors, it was determined that the neurotransmitter norepinephrine causes the premature graying of hair in times of stress.

Hair follicles are innervated by neurons of the sympathetic nervous system. Norepinephrine is released during stress and taken up by melanocyte stem cells – which differentiate into pigment-producing cells – causing premature differentiation and depletion of the reservoir.

In just days, the pigment-producing cells were completely depleted and unable to regenerate, meaning the damage was permanent and the affected follicles were no longer pigmented.

This study provides a unique understanding of the mechanisms by which peripheral neurons regulate stem cells, including how they interact at the cellular and molecular level, an area of research that has previously been lacking.

The team now hopes that this research will form the basis of future studies examining the effects of stress on other organs and tissues, with the aim of preventing the damaging effects of stress.

Hsu concluded: “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.”