The tell-tale sign of aging—gray hair—is something that many women and men have tried to hide for generations. Now, researchers have found that certain stem cells have a unique ability to move within hair follicles, which could maintain the original pigment in the strands.

They found that as our hair ages, sheds, and repeatedly grows back, more of these stem cells become stuck in a compartment called the hair follicle bulge. They remain here and fail to travel back to their original location in the compartment, where proteins would have helped them regenerate into pigment cells—thus helping hairs keep their color.

The study, led by researchers at the NYU Grossman School of Medicine, observed the physically-aged hairs of mice and found that more and more stem cells became stuck when aging. These cells were also found to remain incapable of regenerating or maturing into pigment-producing hairs that keep their color.

The scientists hope the new research may lead to the necessary answers for keeping hair healthy and colored long into old age.

The study focused on cells in the skin of mice which can also be found in humans, called ‘melanocyte stem cells' or McSCs.

Our hair color is controlled by whether non-functional—but continually multiplying—pools of McSCs within hair follicles receive the signal necessary to become mature cells responsible for making the protein pigments.

The NYU study published this week in Nature found the McSCs are ‘plastic' or adaptable, meaning that during normal hair growth, they continually move back and forth on the maturity axis as they move between compartments of the developing hair follicle.

It is inside these compartments that the McSCs are exposed to differing levels of maturity-influencing protein signals, which transform the cells between their most primitive stem cell state to the next stage of their maturation.

The scientists found that increasing numbers of McSCs get stuck—and once stuck, the McSCs remain in the bulge and fail to mature into the transit state that would help them travel back to their original location in the germ compartment where proteins could help them to regenerate into pigment cells.

The researchers say McSC adaptability is not present in other self-regenerating stem cells, such as those making up the hair follicle itself, which are known to move in only one direction along an established timeline as they mature, which helps explain in part why hair can keep growing even while its pigmentation fails.

"Our study adds to our basic understanding of how melanocyte stem cells work to color hair," said the study's lead investigator, Dr Qi Sun, a postdoctoral fellow at NYU Langone Health. "The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans."

"If so, it presents a potential pathway for reversing or preventing the graying of human hair by helping jammed cells to move again between developing hair follicle compartments."

Earlier work by scientists at NYU showed that "WNT signaling was needed to stimulate the McSCs to mature and produce pigment". That study had also shown that McSCs were many trillions of times less exposed to WNT signaling in the hair follicle bulge than in the hair germ compartment, which is situated directly below the bulge.

In the latest experiments, the NYU team ‘physically' aged the hair of mice by plucking them out and forcing them to regrow. The number of hair follicles with McSCs lodged in the follicle bulge increased from 15 percent before plucking to nearly half afterward.

These cells remained incapable of either regenerating or maturing into pigment-producing melanocytes.

The stuck McSCs were found to have ceased their regenerative behavior as they were no longer exposed to enough WNT protein signaling and were unable to produce pigment in new hair follicles, which continued to grow.

In contrast, McSCs which continued to move back and forth between the follicle bulge and hair germ retained their ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire study period of two years.

"It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color," added Dr Mayumi Ito, a Langone Health professor.

"These findings suggest that melanocyte stem cell motility and reversible differentiation are key to keeping hair healthy and colored."

The team now plans to investigate the potential means of restoring the motility of McSCs or physically moving them back to their germ compartment where they can produce pigment—thus stopping hairs from turning gray.

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