Dermatologists have made significant strides in unraveling the mysteries behind gray hair, and are even getting closer to the idea of reversing it.
The key players in this discovery are the melanocyte stem cells (McSCs) residing within hair follicles. These specialized cells are responsible for imparting pigment to both hair and skin. However, to generate the array of pigments that give rise to black, brown, red, and blonde hair, McSCs must continually generate new cells. This crucial pigment production process takes place when McSCs are positioned at the base of the hair follicle, known as the “germ.”
Once their pigment-producing mission is accomplished in the germ, these stem cells undergo a remarkable journey. They migrate back up to the upper region of the hair follicle, referred to as the “bulge,” where they undergo a transformation back into an immature state. This transformation primes them for the next cycle of pigment production.
In a new mouse study, published in the journal Nature on April 19, 2023, if ‘McSC’ get stuck in the bulge, they remain immature and can’t produce enough of the new cells required to produce pigment.’ However, if they aren’t enough, instead of the person’s hair being able to produce its natural hair color, the follicles make gray or white hairs instead.
Study and lead author, Qi Sun, PhD, a postdoctoral researcher who focuses on dermatology at NYU Langone Health in New York City, said, “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.”
According to Dr. Sun, what should happen next is that researchers will need to figure out a better way to understand what causes McSC to ‘move around.’ When they understand that, they could possibly manipulate the stuck cells in these human hair follicles.
Graying Hair Signs of (Stem Cell) Immaturity
What researchers currently comprehend is that melanocyte stem cells (McSCs) do not adhere to the typical behavior exhibited by most other stem cells, which typically progress through maturation until their eventual demise. In the case of McSCs, their maturation process is characterized by fluidity.
Within the intricate structure of hair follicles, various compartments exist, each housing different proteins that influence McSCs to adopt distinct stages of maturity. These stem cells exhibit a unique pattern of mobility, shifting between these compartments, thereby oscillating between stages of maturation, rather than following the linear maturation path commonly observed in other stem cells.
In an investigation led by Dr. Sun and her research team, the behavior of McSCs in graying mice was closely examined. Their findings suggested that McSCs seemed to exhibit signs of fatigue earlier than other stem cell types within the hair follicle.
To uncover this phenomenon, they replicated the natural growth and shedding cycle of human hair by strategically plucking hairs from the mice and subsequently measuring differences between the hairs that regenerated from the plucked follicles and those originating from follicles that had not experienced simulated shedding.
In the “older” regrown hairs, which had undergone plucking, approximately 50 percent of McSCs were found to be retained in the bulge region, in contrast to the younger, unplucked hairs where only 15 percent of MsSCs remained in this stage of development.
This Research Could Help Shed Light On Other Hair Conditions
According to associate professor of dermatology and vice chair for clinical research in dermatology at the University of California Irvine School of Medicine, Natasha Mesinkovska, MD, PhD, the fact that McSCs ‘get stuck in the bulge, of all places, makes sense.’ Notably, she was not involved in the mice study.
She said, “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.”
She also explained that these new findings could probably help dermatologists better understand other types of hair conditions, not only issues with graying hair.
More importantly, the study authors share that graying hair may actually be protective. It seems that the very stem cells responsible for hair pigmentation, known as melanocytes, are the same cells were melanoma, the most lethal type of skin cancer, originates. This underscores the importance of achieving a delicate equilibrium in potential stem cell-based therapies. These therapies would need to activate the stem cells sufficiently to reverse graying, while being careful not to trigger unintended consequences.
“In our quest to make things last forever, we need to do it carefully. We don’t want melanocytes to be super active forever. There’s a reason you don’t let things divide uncontrollably forever,” concludes Dr. Mesinkovska.
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