Loss of hair pigmentation has long been associated with stress; however, stress-related changes at the level of the somatic cell have only recently been elucidated. The hair follicle consists of two stem cell populations: epithelial-derived hair follicle stem cells (HFSCs) and neural crest-derived melanocyte stem cells (MeSCs), which when activated, produce a new hair follicle with pigmentation. Defects in melanin synthesis via loss of differentiated melanocytes or problems in MeSC maintenance can lead to loss of pigmentation in the hair. It has been posited that immune attack from stressors that cause elevated corticosterone and norepinephrine in the blood could be responsible for stress-related hair pigmentation loss.

The innovation: The laboratory of Prof. Ya-Chieh Hsu has uncovered that transient suppression of MeSC proliferation prevents stress-induced hair greying. Increased MeSC loss and hair greying was a response to activation of the sympathetic nerves. When artificial activation of sympathetic nerves with resiniferatoxin (RTX) was administered with buprenorphine, an opioid analgesia, it prevented activation of the sympathetic neurons. Transgenic mice were generated by Dr. Hsu’s lab that were able to artificially activate sympathetic nerves using clozapine N-oxide (CNO). In sites where CNO was injected, it resulted in hair greying. Transient suppression of MeSC proliferation was achieved in Dr. Hsu’s lab through the topical application of cell cycle inhibitors (AT7519 and flavopiridol).

Applications: Understanding the mechanisms of pigmentation loss in hair can give insights into how MeSC loss contributes to aging and whether stress can mimic an accelerated aging process. Use of pain relievers and topical cell cycle inhibitors could be used to reduce hair greying. Therefore, slowing MeSC proliferation is a potential target to treat greying hair and could enable the use of transcriptomic analysis to develop novel treatments for anti-aging.