Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, mela...

Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT‐Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H ₂ O ₂ ) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met‐S=O) repair in the entire gray hair follicle. Accordingly, Met‐S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT‐Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by L ‐ methionine. In summary, our data feed the long‐voiced, but insufficiently proven, concept of H ₂ O ₂ ‐induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.—Wood, J. M., Decker, H., Hartmann, H., Chavan, B., Rokos, H., Spencer, J. D., Hasse, S., Thornton, M. J., Shalbaf, M., Paus, R., Schallreuter, K. U. Senile hair graying: H ₂ O ₂ ‐mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB J. 23, 2065–2075 (2009)

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Oestrogens have significant effects on different cell types important in skin physiology, including the epidermal keratinocytes, dermal fibroblasts and melanocytes. In addition, they can also modulate skin appendages such as the hair follicle, the sebaceous gland and the apocrine glands. Oestrogens may also have important modulatory roles in events such as skin ageing, pigmentation, hair growth, sebum production and skin cancer. It is now recognised that oestrogens can modulate their actions via two distinct intracellular receptors (ERα and ERβ) or via cell surface receptors, which activate specific second messenger signalling pathways. This paper highlights the effects of oestrogens on different components of the skin and reviews some of the more recent developments in terms of receptor expression and cell signalling pathways.