How a stress chemical turns mouse hair gray

It’s a phenomenon common to parents and presidents alike—gray hair brought on by stress. Many heads have prematurely pale tresses, but the biochemistry behind the bleaching is something of a mane mystery. Scientific sleuths, led by Harvard University’s Ya-Chieh Hsu, decided to suss out the biochemical process by studying stress-induced graying in mice. Stress affects the whole body, so the researchers had to figure out which system connected stress to hair color. Experiments eliminated both the immune system and the stress hormone cortisol as suspects. They eventually fingered norepinephrine—a chemical released during times of stress—as the culprit (Nature 2020, DOI: 10.1038/s41586-020-1935-3). This was something of a surprise because adrenal glands produce norepinephrine, but mice that had their adrenal glands surgically removed still went gray with stress. This led Hsu’s team to the sympathetic nervous system, which drives the fight-or-flight response and produces norepinephrine during stressful times. Sympathetic nerves reach into each hair follicle in the skin. When these nerves release norepinephrine, the chemical spurs all stem cells of a certain type to become pigment-producing cells, thereby depleting the reservoir of stem cells that could color hair in the future. Hsu says once those cells are gone, they’re lost forever. The only way that color can be restored is through artificial means, like a good hairdresser.