Ken Inomata/Kanazawa University

Grizzled. Hair turns gray when stem cells incur damage to their DNA.

Gray Hair Signals Battered DNA

If you’ve ever blamed your gray hair on stress, you weren’t far from the truth. Genotoxic stress--the kind that can damage a cell’s DNA--causes hair to whiten over time, according to a new study. The results challenge accepted ideas about how stem cells age and may eventually lead to new ways to prevent graying and treat the more serious conditions caused by genotoxic stress, such as cancer.

For hair, life is simple. A strand grows for several years, then rests for 2 to 3 months before eventually dying and falling out. In 2004, Emi Nishimura, a dermatologist now with the Tokyo Medical and Dental University in Japan, linked this process to the hair follicle’s melanocyte stem cells. As a new hair grows, some melanocyte stem cells become melanocytes, which give the strand its color, while others remain stem cells and store pigment for the next generation of hair. The stem cells continually renew themselves and should theoretically last a lifetime. But over time, the stem cells go missing from hair follicles, leaving people with unpigmented, white hair. How the cells go AWOL remained a mystery.

Nishimura suspected that genotoxic stressors, such as radiation or harsh chemicals, might play a role in the stem cells’ fate, because they’ve been implicated in other signs of aging. She and colleagues at Japan’s Kanazawa University tested the idea in mice, which also gray with age. After exposure to cell-stressing x-rays or chemotherapy drugs, young mice went gray in an unexpected way. More of their melanocyte stem cells matured into color-producing melanocytes, depleting the store of stem cells. Instead of dying or being inactivated, the DNA-damaged cells matured before their time.

“The mature cells lose their regeneration capabilities,” Nishimura explains. “The mice then can’t produce enough pigment-making cells” and consequently go gray. Moreover, the stressed mice’s gray hairs and the cell populations in their follicles were indistinguishable from those of elderly mice, suggesting that genotoxic stress might drive natural graying as well.

The idea isn’t far-fetched, says Ian Jackson, a geneticist at the Medical Research Council in Edinburgh, U.K. “Genotoxic stress happens to everyone over time, and its accumulation is the main cause of aging.” The sun’s ultraviolet radiation, household chemicals, and environmental pollutants can all cause genotoxic stress, as can normal metabolic processes in cells. A single cell in a healthy mammal can suffer as many as 100,000 DNA-damaging events in 1 day, says Nishimura.

“This is a neat study, both for what it tells us about melanocytes and more broadly for what it could mean to stem cell research,” says David Fisher, an oncologist at Harvard Medical School in Boston. “We normally think of graying as an undesirable thing, but this work suggests it could be protective,” ridding the body of potentially dangerous damaged cells by preventing their further division. Future studies should explore whether stem cells elsewhere in the body undergo a similar premature maturation, he says. Tapping into this natural defense mechanism might enable researchers to prevent cancers like melanoma, which results from DNA damage to melanocytes in the skin, adds Jackson.

The results, published in tomorrow's issue of Cell, might also lead to new measures for preventing gray hair by modulating the DNA damage response. What they won’t do is support the still-unproven common claim that emotional stress causes graying--at least not yet, says Fisher. “With this mechanistic insight,” he notes, “we might finally be able to look at questions like that one.”

Posted in Biology