Question: Many people who meet us will remark on how similar my brother and I look, possibly even mistaking the two of us on occasion. One significant difference between the two of us is immediately obvious: while my brother has been sporting a near full head of gray hair since high school, I have maintained my luscious black locks. What is the biomolecular pathway that causes the graying of hair?

Answer: In their 2011 article on the biochemistry of hair pigmentation, Schallreuter et al. suggest that hydrogen peroxide, or H2O2 leads to gray hair through a multitude of pathways. Accumulation of hydrogen peroxide can affect antioxidant machinery, tyrosinase activity in melanogenesis, and cAMP signaling, among other mechanisms.

Under normal conditions, hydrogen peroxide is split to H2O (water) and O2 by catalase. Higher than normal concentrations of hydrogen peroxide and metals lead to hydroxyl radicals which oxidize methionine and tryptophan, deactivating catalase. Low catalase activity is linked to both vitiligo and gray hairs. The decrease in catalase activity causes deleterious effects on tyrosinase, an important enzyme in melanogenesis (the formation of the hair and skin pigment known as melanin). In turn, these effects on tyrosinase also affects tyrosine concentrations, causing a decrease in melanogenesis and hair color.

Hydrogen peroxide also affects levels of POMC-derived peptides, which target skin and hair follicles, by reducing POMC processing. This in turn leads to decreased concentrations of these POMC peptides ACTH, alpha and beta MSH as well as beta-endorphin, which have roles in pigmentation and regulation of cAMP, which upregulates tyrosinase. Due to the low concentrations of the POMC peptides, cAMP synthesis decreases, leading to lower activities of cAMP and tyrosinase leading to graying hair.

As seen, increased hydrogen peroxide concentration overall leads to the decrease of tyrosinase through decreased cAMP levels and catalase activities. These two pathways work separately to inhibit tyrosinase, the enzyme directly linked to melanogenesis. For more information and further details, refer to the Schallreuter et al. paper.

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Sources:

Schallreuter et al “The redox – biochemistry of human hair pigmentation.” Pigment Cell & Melanoma Research, 24 (2011): Web. 30 June 2016. Doi: 10.1111/j.1755-148X.2010.00794

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