The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates multiple physiological functions, ranging from nutrient sensing and metabolism to proliferation and senescence. In cell culture, mTORC1 inhibition can promote pigmentation, while its role in human hair follicle (HF) biology remains unknown. Since patients with a loss-of-function mutation of the key endogenous inhibitor of mTORC1 activity, tuberous sclerosis complex (TSC), show defective hair pigmentation (poliosis), we probed the hypothesis that mTORC1 regulates human HF pigmentation. Interestingly, grey/white HFs exhibit significantly increased mTORC1 activity (measured by p-S6). We next treated healthy, organ-cultured human scalp HFs with the key mTORC1 inhibitor, rapamycin (RPM), and observed a significant increase in HF melanin production, gp100 expression, tyrosinase activity and the dendricity of gp100+ HF melanocytes. RPM also in increased the production of melanotropic a-MSH in both pigmented and graying HFs, and even re-stimulated melanogenesis in grey HFs were some gp100+ cells were still present. In contrast, excessive intrafollicular mTORC1 activity induced by TSC2 knockdown significantly reduced HF pigmentation. We are now examining whether the HF pigmentation-stimulatory effect of RPM is indeed aMSH-dependent. Moreover, rapamycin prolonged anagen duration in pigmented and grey/white HFs ex vivo, thus expanding the window of opportunity for repigmenting gray hair (canities), which can only occur during anagen. This study introduces mTORC1 activity as an important physiological regulator of human hair pigmentation and invites one to explore RPM as anti-greying agent.

ESDR518 - Nutrient and stress sensing as novel physiological regulator of human hair pigmentation and greying: Role of mTORC1 activity

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.