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

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