650 Controlling mTORC1 activity as a novel therapeutic strategy for managing human hair growth and pigmentation

The mechanistic Target of Rapamycin Complex 1 (mTORC1) exerts multiple physiological functions, including nutrient sensing and the control metabolism, proliferation, senescence Wnt signaling. Yet, role mTORC1 activity in human hair follicle (HF) biology remains unknown. Since patients with a loss-of-function mutation key endogenous inhibitor activity, tuberous sclerosis complex (TSC), can show poliosis, we probed hypothesis that regulates HF pigmentation, using organ culture. When healthy anagen scalp HFs were treated ex vivo inhibitor, rapamycin, this significantly stimulated melanin production, gp100 expression, tyrosinase dendricity gp100+ melanocytes. Interestingly, was associated increased production a-MSH by keratinocytes, notably graying HFs, some which rapamycin even re-stimulated melanogenesis. In contrast, excessive intrafollicular induced TSC2 knockdown reduced pigmentation. (Of note, provides first siRNA assay system for functionally interrogating unclear TSC physiology). Moreover, prolonged inhibited matrix keratinocyte apoptosis vivo, thus expanding window opportunity repigmenting gray hair, only occur during anagen. Thus, here plays fundamental both, pigmentation cycling. This invites one to explore rapalogs management growth disorders.