602 mTORC1 activity controls human scalp hair follicle pigmentation and growth

The mechanistic Target of Rapamycin Complex 1 (mTORC1), whose activity is inhibited by rapamycin (Rapa), a multiprotein complex that senses nutrients, growth factors and cellular stressors, regulates multiple processes including proliferation, autophagy, Wnt signaling. Since loss-of-function mutations the key endogenous inhibitor mTORC1 activity, tuberous sclerosis (TSC), are associated with hair depigmentation (poliosis), we asked whether also impacts on human follicle (HF) pigmentation. Interestingly, pharmacological inhibition Rapa in organ-cultured, healthy scalp anagen VI HFs, lead to prolongation up-regulation matrix keratinocyte while apoptosis was significantly down-regulated (indicating “window opportunity” for anti-greying treatment). Furthermore, HF melanogenesis, gp100 expression, number dendricity gp100+ melanocytes were up-regulated HFs cycle-independent manner. Our preliminary data suggest treatment can even partially restimulate pigmentation some greying ex vivo. In contrast, TSC2 silencing vivo induced hyperactivation reduced melanogenesis. summary, provide first evidence mTOR an important, previously unappreciated physiological regulator Thus, inhibiting intrafollicular rapalogs may become attractive novel intervention strategy future management greying, alopecia.