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Off-color. The loss of stem cells turns mice grey.

Three Gray Mice

Instead of colorant, hair dyes of the future should perhaps contain a "stem cell rejuvenator." That's one implication of a study, published online this week in Science, that shows mice--and possibly people--get gray hair because of a decline in pigment-producing cells.

Stem cells are long-lasting suppliers of new cells for a variety of tissues throughout the body, and hair is no exception. Several years ago, scientists discovered stem cells that replenished pigment-making cells, called melanocytes, in hair follicles. After they're formed, melanocytes migrate to the bottom of the hair follicle, where they give off a person's characteristic hair color to keratinocytes that make up a hair.

To find out why this process falters later in life, molecular oncologist David Fisher of Harvard Medical School and colleagues used two mouse mutants with hair problems of their own. One goes white in 6 to 10 months thanks to a mutation in a gene called Mitf. The other, with a mutation in the BcI2 gene, goes gray a few weeks after birth. To facilitate the study, the researchers used mice that produce an easily detectable protein in their melanocytes and melanocyte stem cells. They also studied aging human hair follicles.

They discovered that stem cells were gradually disappearing as the mice turned gray; in their place, melanocytes cropped up, but failed to migrate down, where they are supposed to do the coloring. In other words, stem cells were failing to make more of themselves, and the melanocytes they produced weren't behaving properly. "Something in aging [mutant] mice was causing the stem cell to lose its 'stemness'," says Fisher.

When the team looked in normal old mice, they saw the same, misplaced melanocytes cells taking up the space that stem cells vacated. And when they turned to humans, they discovered misplaced melanocytes in middle-aged people. Moreover, the elderly had neither stem cells nor melanocytes. That suggests the mechanism behind hair color loss is similar in mice and humans.

"The work is telling us that these [melanocyte] stem cells don't have an infinite capacity for self-renewal," says geneticist Ian Jackson of the Medical Research Council Human Genetics Unit, U.K. If the cells merely stopped working, preventing gray hair would be relatively straightforward, he says: "We could turn them back on." How to prevent their loss may be more difficult, he adds. So don't throw away your dye just yet.

Related Sites
David Fisher's website
More on hair growth