Grey Hair: A Sign of Wisdom or a Sign of Stress?
Background
Stem cells have been a hot topic in science for many reasons. They can be used for regeneration of all types of cells, which is why their population in the body is extremely important. The body maintains its stem cells in a stem cell niche, which is essentially a nursery for them. However, sometimes things like stress can affect the ability of that niche to protect the stem cells and results in stem cell depletion. There are some stem cells that are involved in hair pigmentation. Have you ever wondered why certain people experience hair-greying sooner than others? That’s due to hyperactivation of the sympathetic nervous system, or chronic high stress levels. The paper, Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells, explores this idea using mice. The body reacts to stressful situations by releasing hormones like adrenaline/noradrenaline (fight or flight response) and cortisol via the adrenal gland. Two types of stem cells that play a vital role in maintaining hair pigment are hair follicle stem cells (HFSCs — in epithelial tissue) and melanocyte stem cells (MeSCs — in the neural crest). MeSCs are the key players in hair pigmentation because they give rise to melanocytes, which are cells that produce melanin. Yes, the same chemical that creates a nice summer tan also contributes to your hair color! When MeSCs are activated, they proliferate (or divide) and then begin to differentiate and serve their purpose as mature melanocytes.
Summary: Inducing Stress in Mice Causes Hair-greying
Scientists induced stress in mice and observed their resulting hair color. Different mice were exposed to different types of stresses: restraint stress, chronic unpredictable stress, and nociception-induced stress. To induce restraint stress, mice were kept in a restrainer for four hours a day. Stressors that were randomly rotated for chronic unpredictable stress consisted of a tilted cage, isolation, damp bedding, rapid light and dark changes, restraint, an empty cage, and changing their cage. Lastly, nociceptors are exclusively for pain recognition. Resiniferatoxin (RTX) was injected into mice to induce a burning feeling, like the chemical in chili peppers that makes them spicy. Whenever mice experienced these stressors, their stress hormone levels increased, indicating activation of the sympathetic nervous system.
To first determine the effect of stress on the mice, scientists injected them with RTX (and a pain killer to isolate the effect of nociceptive sensory neurons). By inhibiting the mental recognition of pain, the stress response of the physical effect of pain is isolated. Basically, they are preventing the mice from reacting to the pain. The injection resulted in fewer MeSCs present in the hair follicles such that the next time hair grew, it was grey. Without MeSCs to produce melanocytes and without melanocytes to produce melanin, the hair lacks pigment and appears grey (Figure 1B and 1D).
Now that they determined stress depletes MeSCs, they tried to isolate the sympathetic nervous system. Since the adrenal gland is the main noradrenaline source, the adrenal glands of some mice were removed to examine the effect of stress hormones in hair greying. Noradrenaline was still produced in mice without adrenal glands because stress (induced by injection of RTX) activated the sympathetic nervous system. Interestingly, the neurons unique to this system also have the ability to produce noradrenaline, still causing hair greying in the mice. Additionally, a different experiment was performed where injection of a neurotoxin that destroys sympathetic nerves followed injection of RTX. Hair greying was prevented in these mice because the sympathetic nervous system was incapable of being activated.
The significant role of noradrenaline was also illustrated in another experiment: hair greying was prevented in mice that were injected with both RTX and guanethidine — an inhibitor of the release of noradrenaline from sympathetic nerve endings. When mice were injected with either RTX or noradrenaline, proliferative MeSCs increased in number. Proliferation of MeSCs depletes their existence because they begin to differentiate, which basically pushes them further along in their lifespan. These results indicate that activation of the sympathetic nervous system — stress — causes both MeSC depletion and consequently, hair-greying.
