From the National Institutes of Health

Stress can have a variety of negative effects on the body. The idea that acute stress can cause hair to turn gray is a popular belief. But until now, that link wasn’t scientifically proven.

Hair color is determined by cells called melanocytes, which produce the pigment melanin. New melanocytes are made from melanocyte stem cells that live within the hair follicle at the base of the hair strand. As we age, these stem cells gradually disappear. The hair that regrows from hair follicles that have lost melanocyte stem cells has less pigment and appears gray.

Researchers set out to determine if stress could also cause hair to gray, and if so, how. The study was funded in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other NIH components. The findings appeared in Nature on January 22, 2020.

The research team, led by Dr. Ya-Chieh Hsu of Harvard University, used mice to examine stress and hair graying. The mice were exposed to three types of stress involving mild, short-term pain, psychological stress, and restricted movement. All caused noticeable loss of melanocyte stem cells and hair graying.

Having established a link between stress and graying, the scientists then explored several potential causes. They first tested whether immune attack might be responsible for depleting melanocyte stem cells. But stressing mice with compromised immune systems still led to hair graying. The team then investigated the role of the stress hormone corticosterone, but altering its levels didn’t affect stress-related graying.

The researchers eventually turned to the neurotransmitter noradrenaline, which, along with corticosterone, was elevated in the stressed mice. They found that noradrenaline, also known as norepinephrine, was key to stress-induced hair graying. By injecting noradrenaline under the skin of unstressed mice, the researchers were able to cause melanocyte stem cell loss and hair graying.

Noradrenaline is produced mostly by the adrenal glands. However, mice without adrenal glands still showed stress-related graying. Noradrenaline is also the main neurotransmitter of the sympathetic nervous system, which is responsible for the “fight-or-flight” reaction in response to stress.

The team ultimately discovered that signaling from the sympathetic nervous system plays a critical role in stress-induced graying. Sympathetic nerves extend into each hair follicle and release noradrenaline in response to stress. Normally, the melanocyte stem cells in the follicle are dormant until a new hair is grown. Noradrenaline causes the stem cells to activate.

Using florescent labelling, the researchers observed the stem cells change to melanocytes and migrate away from their reserve in the hair follicle. With no remaining stem cells, no new pigment cells can be made, and any new hair becomes gray, then white. 

“When we started to study this, I expected that stress was bad for the body — but the detrimental impact of stress that we discovered was beyond what I imagined,” Hsu says. “After just a few days, all of the melanocyte stem cells were lost. Once they’re gone, you can’t regenerate pigments anymore. The damage is permanent.”

The authors highlight the need to further study the interactions between the nervous system and stem cells in different tissues and organs. The knowledge gained in this work will be useful in future investigations into the impact of stress on the body and the development of new interventions.