Aging isn’t kind to our bodies—or our hair. As we get older, the cellular machinery that regenerates our crowning glory slows, causing it to thin and disappear. Now, scientists have uncovered a new mechanism behind hair loss: When stem cells in hair follicles are damaged by age, they turn themselves into skin. Over time, this happens to more and more stem cells, causing hair follicles to shrink and eventually disappear.
This is the first time such a switch has been associated with aging in any tissue, says Emi Nishimura, a biologist at Tokyo Medical and Dental University who led the study.
Stem cells—precursor cells that can give rise to specialized cells like skin and hair—regenerate throughout the life of an organism and are located all over the body. But unlike stem cells in the blood or intestinal lining, hair follicle stem cells regenerate on a cyclical basis. Their active growth phase is followed by a dormant phase, in which they stop producing hair. These discrete on-off periods make hair follicle stem cells a useful model for studying stem cell regulation—and hair loss.
“Previously, people knew that when we age, the hair becomes thinner,” says Cheng-Ming Chuong, a biologist at the University of Southern California in Los Angeles who was not involved in the work. But at the cellular and molecular level, “there’s not enough understanding.”
To figure out why hair thins in old age, Nishimura and her colleagues started with mice. They looked at hair follicle stem cell growth cycles in live animals—a daunting task—and found that age-related DNA damage triggers the destruction of a protein called Collagen 17A1. That in turn triggers the transformation of stem cells into epidermal keratinocytes, they report today in Science. In their new state, the damaged stem cells slough off easily from the skin’s surface.
“When damaged cells deplete that niche of Collagen 17A1, they alter their own signaling environment,” says Maksim Plikus, a biologist at the University of California, Irvine, who was not involved in the study. He calls it “interesting” that these damaged cells “change their fate” rather than committing suicide through apoptosis (programmed cell death) or stopping cell division through senescence.
To see whether their results carried over to people, Nishimura and her team analyzed hair follicles in scalps from women aged 22 to 70. They found that follicles in people over 55 were smaller, with lower levels of Collagen 17A1. “We assume that … aging processes and mechanisms [similar to those in the mice] explain the human age-associated hair thinning and hair loss,” Nishimura says. She adds that Collagen 17A1 could be a target for hair loss treatments—although stem cell depletion is unlikely to be the only factor behind the condition.
The new study adds to a growing body of work that examines the cellular and molecular mechanisms of stem cell regulation. Another study published today—also in Science—finds that a transcription factor called Foxc1 could also help regulate the hair growth cycle.
Rui Yi, a biologist at the University of Colorado, Boulder, and colleagues found that the transcription factor was expressed in active hair follicle stem cells, but not in inactive ones. When they bred mice without Foxc1 in their skin, the activated stem cells didn’t go back into the dormant, or quiescent, state. After further testing, they concluded that active cells produce Foxc1 to temporarily “deactivate,” thus keeping their regeneration in check.
“After the cells start to duplicate, they say, ‘mission accomplished, let’s go back to quiescence. Let’s wait for the next time,’” Yi says. This suggests that stem cells can sense their state and respond appropriately.
Together, the two studies highlight that within the past 15 years, hair follicle stem cells have become a tractable model for studying stem cell behavior, Plikus says. Now, scientists are starting to unlock the underlying molecular machinery. Says Chuong: “These two papers sort of represent the beginning of these new efforts.”