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Gray hair in old age: Hydrogen peroxide inhibits the synthesis of melanin

Researchers from Mainz and Bradford discover the molecular mechanism for hair turning white and gray in old age

Gray or white hair develops with advancing age in an entirely natural aging process which results in the generation of less and less color pigments.

Researchers of the Johannes Gutenberg University Mainz in Germany und the University of Bradford in Great Britain have now unlocked the secret of hair turning white or gray in old age. According to them, free oxygen radicals are significantly involved in the loss of hair color. "The originator of the entire process is hydrogen peroxide, which we also know as a bleaching agent," explains Professor Heinz Decker of the Institute of Biophysics at Mainz University.

"With advancing age, hydrogen peroxide builds up in larger amounts in the hair follicle and ultimately inhibits the synthesis of the color pigment melanin." The biophysicists in Mainz together with dermatologists from Bradford have revealed the molecular mechanisms of this process for the first time, and they published their findings in the professional journal The FASEB Journal.

Hydrogen peroxide - or H2O2 by its the chemical formula - is a by-product of metabolism, and as such it is generated in small amounts throughout the human body, conse-quently also in hair follicles. With increasing age, the quantity builds up, because the human body can no longer keep up neutralizing the hydrogen peroxide using the enzyme catalyse, which breaks down hydrogen peroxide into its two components water and oxygen. In their work, the scientists showed that in aging cells this enzyme is still present but in very limited concentration. This has dramatic consequences. Hydrogen peroxide attacks the enzyme tyrosinase by oxidizing an amino acid, methionine, at the active site. As a consequence, this key enzyme, which normally starts the synthesizing pathway of the coloring pigment melanin, does not function anymore.

"We now know the specific molecular dynamic that underlies this process," elucidates Decker. The scientists at the Institute of Biophysics at Mainz University have been working for about ten years already on research concerning tyrosinases, which are enzymes present in all organisms and performing a variety of functions. In computer simulations that helped to reveal the molecular mechanisms, the biophysicists were supported by the newly established research focus on "Computer-based Research Methods in the Natural Sciences" at Johannes Gutenberg University Mainz.

Oxidation by hydrogen peroxide not only interferes with the production of melanin, but also inhibits other enzymes that are needed for the repair of damaged proteins. As a re-sult, a cascade of events is set off, at the end of which stands the gradual loss of pig-ments in the entire hair from its root to its tip. With this research work, the scientists from Mainz and Bradford not only solved - on a molecular level - the age-old riddle of why hair turns gray in old age, but also have pointed out approaches for future therapy of vitiligo, a skin pigment disorder. For melanin is not only the pigment in hair, but it is also responsible for color in skin and eyes.

The researchers in Mainz were supported by the Collaborative Research Center 490 "Mechanisms of Invasion and Persistence of Infectious Agents," and the Research Training Group 1043 "Antigen-specific Immunotherapy", both funded by the German Research Foundation (DFG).

Original Publications:
J. M. Wood, H. Decker, H. Hartmann, B. Chavan, H. Rokos, J. D. Spencer, S. Hasse, M. J. Thornton, M. Shalbaf, R. Paus, and K. U. Schallreuter
Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunt-ing methionine sulfoxide repair

The FASEB Journal, online published on 23 February 2009, doi: 10.1096/fj.08-125435

T. Schweikardt, C. Olivares, F. Solano, E. Jaenicke, J.C. Garcia-Borron and H. Decker
A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations

Pigment Cell Research (2007) 20:394-401

H. Decker, T. Schweikardt and F. Tuczek
The first crystal structure of tyrosinase: all questions answered?
Angewandte Chemie International Edition Engl., (2006) 45, 4546 - 4550

Petra Giegerich | idw
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