The phenomenon of accelerated graying from stress is caused by the loss of stem cells in the hair follicles. This is the conclusion reached by scientists who injected mice with a toxin and monitored the condition of their skin. They found that under stress, the melanocyte precursor cells disappear from the follicles, and norepinephrine mediates this process. The work was published in the journal Nature.
In the literature, there are often stories that a character "turned gray overnight." So, for example, they talked about the Empress Marie Antoinette, who allegedly turned gray after her escape during the French Revolution failed. Despite the fact that these stories do not always look believable, doctors have indeed described several times in people the phenomenon of accelerated graying (aka Marie Antoinette's syndrome).
Stress is commonly cited as the cause of this dramatic graying, but it is still unclear exactly how stress affects the hair. It can be assumed, for example, that it is the melanocyte cells that give the hair color. They are formed next to the hair follicle from the corresponding stem cells. Stress can destroy the melanocytes themselves, their progenitor cells, or only the melanin pigment.
Bing Zhang of Harvard University and his colleagues decided to look into this issue, because they are interested in tissue regeneration and how it changes under stress. The researchers worked with black laboratory mice. To find the optimal stress conditions for graying, three groups of mice were placed in different stressful situations.
The first group got immobilization: the animals were placed in a cramped cage for several hours or several days. The second group was exposed to chronic unpredictable stress: rocking of the cell, a sharp change in illumination, transplantation from cell to cell, immobilization, and so on. The third group got physiological stress: the animals were injected with resiniferatoxin, an analogue of capsaicin from hot pepper. Then the mice were shaved bald to accelerate hair growth, and it was calculated at what percentage of the total area gray hair would grow. The most effective way to induce graying turned out to be the latter: after injections, almost 30 percent of the animal's skin was covered with gray hair. True, this did not happen overnight, as they write in the books, but in a couple of weeks - so much time is needed to change one generation of hair in mice.
Normal and gray from a prick mouse
Scientists have verified that under the influence of the toxin, the mice really experienced physiological stress: the concentration of corticosterone in their blood increased threefold, and norepinephrine - tenfold. They then confirmed that the stress and graying were caused by the toxin: they injected the mice with an analgesic and found that the hormone levels did not differ from the control group (which did not receive the toxin), and gray hair covered only a few percent of the skin (compared to 30 percent - without analgesic).
To find out which cells are affected by stress, scientists injected the toxin into animals in the late stages of follicular growth. At this moment, mature melanocytes are already formed in the hair, and the stem cells are located separately - in a bag next to the follicle. After the injection of the toxin, mature melanocytes continued to produce melanin, but stem cells became five times less. Thus, the scientists found that stress does not affect the "finished" hair, but only the production of new pigmented cells.
In the next phase of the work, the researchers looked for a mediator between stress and stem cells. Such could be, for example, immune cells - however, mutant mice, deprived of various elements of the immune system, turned gray just like ordinary animals. Corticosterone and norepinephrine could also act as mediators. However, the artificial increase in the level of corticosterone did not make the animals turn gray, unlike norepinephrine: when it was injected under the skin of the animals, even in the absence of painful injections, the hair lost pigmentation at the injection sites.
Norepinephrine can enter tissues from two sources. The first is the adrenal glands, the second is the sympathetic nerve fibers. When scientists injected the toxin into mice with removed adrenal glands, the animals still turned gray. Therefore, the researchers hypothesized that the hair follicles "learn" about stress from the sympathetic nervous system. Indeed, when the animals were injected with a neurotoxin that destroys sympathetic fibers, they stopped turning gray in response to painful stress.
Finally, the researchers figured out what happens to stem cells in response to stress. Having stained the hair follicles of animals that received a painful injection, they noticed that the preparations showed no traces of stem cell death or DNA damage in their nucleus. On the contrary, cells were actively dividing or moving.
Based on the results of the experiments, the authors of the work built the following chain of events: when a stress factor acts on the body, sympathetic nerve fibers react to it. They release norepinephrine, which causes stem cells, the precursors of melanocytes, to divide and migrate. Apparently, this is the reason for the loss of pigmentation: normally stem cells must be in a certain place of the follicle and rarely multiply. When they divide too often, their resources are depleted, and in the process of migration they often leave the follicle, and as a result cannot replenish the supply of melanocytes. The authors of the work note that in the future it would be interesting to check whether these processes are involved in the "planned", age-related loss of hair pigmentation.