Researchers have identified the mechanism for why hair goes gray with age and stress -- and in the process discovered a novel response to DNA damage in stem cells, they report in the June 12 issue of Cell.

It's generally thought that accumulated DNA damage is a likely culprit in aging phenotypes such as graying hair, but researchers have been unable to show a direct link, said David Fisher chairman of the department of dermatology at the Massachusetts General Hospital, who was not involved in the study. "Hair follicles are very deep," said Fisher, so it's unlikely that DNA damage would be caused by UV radiation from sunlight, for example.

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In order to understand the process involved in graying hair, Emi Nishimura from the Kanazawa University in Ishikawa, Japan, and colleagues investigated the role of ionizing radiation and other chemical inducers of DNA damage on pigment stem cells called melanocyte stem cells (MSCs) in mice. All the measures of DNA damage they studied resulted in premature graying in mice.

To probe the cellular mechanism involved, the researchers took a closer look at the stem cell niche at the base of the hair follicle. "DNA damage normally causes two outcomes -- apoptosis or cell cycle arrest," said Peter McKinnon from St. Jude Children's Research Hospital in Memphis, Tenn., who was not involved in the research. Nishimura and colleagues, however, found a third pathway -- an increase in differentiated melanocytes. Rather than causing the stem cells to die, DNA damage appeared to force MSCs into terminal differentiation. As a result, they lost their ability to continue to replenish pigmented cells.

Like apoptosis or senescence, "differentiation is a protective mechanism," said Fisher. Cells that have been subjected to DNA damage have a higher likelihood of becoming cancerous. Terminal differentiation in these cells, much like senescence and apoptosis, results in the cells' death. Thus, said Fisher, graying could simply be the body's mechanism for removing damaged stem cells before they have a chance to become cancerous.

If the differentiation proves to be a response to DNA damage in other cell types as well, said Fisher, it could open up a new area of study in cancer research. Scientists have extensively studied the links between cancer and apoptosis, he explained, but "if you're looking for errors [that lead to cancer] in a differentiation pathway, you're looking in a very different place."

Correction (12 June 2009): The original version of this article referred to Emi Nishimura as a male. Nishimura is a female. The Scientist regrets the error.


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