‘Stuck’ Stem Cells Appear to Cause Graying Hair

Dermatologists are one step closer to understanding what causes gray hair — and potentially one day being able to reverse it.

Stem cells that live in the hair follicle, called melanocyte stem cells (McSC), are responsible for the pigment that colors hair and skin. But to produce that pigment — black, brown, red, and blonde — McSCs need to produce more cells. And in order to do this, they need to be at the bottom of the hair follicle, called the germ, to produce pigment. After that, stem cells migrate back to the top of the hair follicle, called the bulge, where they revert back to their immature state and get ready to start the process over again.

According to a new mouse study, published April 19, 2023, in the journal Nature, if McSC get stuck in the bulge, they remain immature and can’t produce enough of the new cells required to produce pigment. If there aren’t enough, instead of a person’s natural hair color, the follicles will produce gray or white hairs.

“One ramification of our study could be to figure out how to mobilize those stuck stem cells in the bulge to go to the hair germ compartment where they can participate in the regeneration of mature cells that can produce pigment,” says Qi Sun, PhD, a postdoctoral researcher who focuses on dermatology at NYU Langone Health in New York City, who led the study.

Dr. Sun says that next, researchers will need to work to better understand what causes McSC to move around. If they understand that, they may one day be able to manipulate the stuck cells in human hair follicles.

Gray Hair Is a Sign of (Stem Cell) Immaturity

What researchers do currently understand is that melanocyte stem cells don’t behave like most other stem cells, which mature until they die. For McSC, maturation is fluid.

Hair follicles contain many different compartments, all with different proteins that prompt McSC to be in different stages of maturity. By moving around these compartments, they move back and forth between stages of maturation, rather than maturing in a linear way like most stem cells do.

When Sun and her team studied the phenomenon in the hair of graying mice, they found that McSC appeared to tire sooner than other stem cells in the hair follicle.

To discover this, they simulated the natural growth and shedding of human hair, by strategically plucking hairs on the mice and measuring differences between the hairs that regenerated from the plucked follicles and those produced by follicles that had not simulated shedding.

In plucked — or “older” — regrown hairs, 50 percent of McSC were stuck in the bulge, compared with 15 percent in the younger, unplucked hairs.

Research Could ‘Shed’ Light on Other Hair Conditions

The fact that McSCs get stuck in the bulge, of all places, makes sense, says Natasha Mesinkovska, MD, PhD, an associate professor of dermatology and vice chair for clinical research in dermatology at the University of California Irvine School of Medicine. Dr. Mesinkovska was not involved in the mice study.

“The bulge is very immune-protected. In certain diseases, they get attacked and lose this immune privilege, which is what we believe is what causes alopecia,” Mesinkovska tells Everyday Health, noting that the new findings could help dermatologists better understand other hair conditions, not just graying.

Importantly, the study authors also noted that graying hair may be protective. The same stem cells involved in hair pigmentation, melanocytes, are also where melanoma, the deadliest form of skin cancer, forms. This means that if stem cell–related therapies are developed, they’ll need to strike a delicate balance between activating stem cells enough to reverse grays, but not so much that it causes unintended consequences.

“In our quest to make things last forever, we need to do it carefully,” Mesinkovska says. “We don’t want melanocytes to be super active forever. There’s a reason you don’t let things divide uncontrollably forever.”