The Italian researchers who identified the apparent hair growth effects of an oral combination of Resveratrol and Curcumin stated rather nonspecifically in their patent application that Resveratrol by itself helped modify the hormonal environment in a way that was favorable for hair growth. Since Resveratrol is an established activator of Sirtuin 1, this study identifies a mechanism by which Resveratrol *may* do just that.
Mol Cell Biol. 2006 Nov;26(21):8122-35. Epub 2006 Aug 21
Hormonal control of androgen receptor function through SIRT1
Fu M, Liu M, Sauve AA, Jiao X, Zhang X, Wu X, Powell MJ, Yang T, Gu W, Avantaggiati ML, Pattabiraman N, Pestell TG, Wang F, Quong AA, Wang C, Pestell RG
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.
Over the past decade, SIRT1 has been the most investigated gene involved in diverse cellular functions. In the case of Androgen mediated disorders such as acne, BPH, and MPB, SIRT1 binds to and deacetylates the androgen receptor and represses dihydrotestosterone-induced androgen receptor signaling in humans.
The link betweenSIRT1 and both cancer, aging and androgen mediated disorders provide new insight into the therapeutic potential of small molecule activators or specific targets of SIRT1 for their prevention and treatment.
Resveratrol is a SIRT 1 activator that produces the same health benefits as Caloric restriction, which reliably prevents and/or corrects age related hair loss in rat studies.
SIRT1 has dependent diseases. One consistent observation has been that calorie restricted rats have robustly healthy coats of fur compared to controls. The SIRT1 activator resveratrol mimics the health benefits of CR and has emerged as a major drug development target for treating age-related disorders and aging in general.