title: Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair.
abstract: 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.
authors.affiliation: Clinical and Experimental Dermatology/Department of Biomedical Sciences, University of Bradford, Bradford, BD7 1DP, West Yorkshire, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Wood
authors.forename: H
authors.initials: H
authors.lastname: Decker
authors.forename: H
authors.initials: H
authors.lastname: Hartmann
authors.forename: B
authors.initials: B
authors.lastname: Chavan
authors.forename: H
authors.initials: H
authors.lastname: Rokos
authors.forename: J D
authors.initials: JD
authors.lastname: Spencer
authors.forename: S
authors.initials: S
authors.lastname: Hasse
authors.forename: M J
authors.initials: MJ
authors.lastname: Thornton
authors.forename: M
authors.initials: M
authors.lastname: Shalbaf
authors.forename: R
authors.initials: R
authors.lastname: Paus
authors.forename: K U
authors.initials: KU
authors.lastname: Schallreuter
mesh_terms: D000375:Aging; D002374:Catalase / Q000032:analysis; D006200:Hair Color; D018859:Hair Follicle / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008715:Methionine / Q000031:analogs & derivatives* / Q000032:analysis / Q000172:deficiency; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration
chemical_list: D017382:Reactive Oxygen Species; D008715:Methionine; D006861:Hydrogen Peroxide; D002374:Catalase; C013111:methionine sulfoxide