Gray hair is one of the most recognizable features of old age. For most people, gray hair is inevitable. No matter how many times you attempt to dye your hair, the roots will continue to grow out gray because the cells responsible for pigmenting new growth have stopped working properly. Now, thanks to a recent study published in Nature, we are now one step closer to uncovering why hair color fades with age, and most importantly, how we may be able to reverse it.
The structure of a single hair is much more complex than what you can see growing from your head. Each strand is anchored in a hair follicle, an opening in the skin that extends several layers. Hair grows outwards from the base of the hair follicle in a region known as the hair germ. Here, specialized hair follicle stem cells coordinate the growth of new hair. Like any other stem cell, these cells have the unique ability to not only preserve themselves through regeneration but also give rise to daughter cells that, under the right conditions, can mature into any cell type.
Hair color is determined by another type of stem cell embedded in the hair follicle that produces melanocytes. Depending on the shade of your hair, melanocytes produce different types of melanin to give your hair its color. The more melanin, the darker your hair color. When the regenerative properties of melanocyte stem cells begin failing, hair appears to turn gray.
Normally, most stem cells involved in hair growth are housed in the hair follicle’s bulge region, just above the hair germ. At the beginning of the growth phase, hair follicle and melanocyte stem cells begin dividing to birth new daughter stem cells. These cells then travel to the hair germ, where the presence of growth factors encourage them to mature and harden into new hair cells. As hair grows, color is simultaneously added.
With time, melanocyte stem cells seem to start failing earlier than their hair follicle counterparts. For some, gray hairs may start appearing in their early twenties, but most people do not have significant gray hair until the age of 50. Understanding what causes melanocyte stem cells to fail so early may finally provide insight into why some people begin to go gray earlier than others.
For their study, Sun et al. used 3D imaging to track the movement of melanocyte stem cells in mouse hairs. It was previously thought that the process through which stem cells mature into melanocytes was irreversible. Sun et al., however, found that the activity of these cells was much more dynamic.
Their observations revealed that stem cells located in the bulge region generate daughter melanocyte stem cells that then pool at the base of the hair germ. Once the growth phase is initiated, these cells have one of two fates. They either remained in the hair germ and matured into pigment-producing melanocytes, or they traveled up towards the bulge region to continue their journey as stem cells. However, when investigators took a closer look at the structure of the traveling cells, they were surprised to find that these cells had already begun the process of maturing into melanocytes. Somehow these cells seemed to be reverting backwards. This even included cells that were only a couple steps away from becoming fully functioning melanocytes.
What triggers this reversal? To answer this question, we must consider the type of environment that stem cells are exposed to in the hair germ vs. the bulge region. As the primary site for growth, the hair germ enables molecular signaling to create just the right environment for melanocyte stem cells to grow into mature cells. If one of these cells finds itself in the hair bulge before this process can be completed, it no longer has the resources to continue down this path. Rather than dying, these cells simply go back to their initial stem cell state. When the hair growth phase ends, many, though not all, of the melanocyte stem cells that traveled to the hair bulge return to the hair germ, where the whole process can begin again.
Since the average hair cycle only lasts about 3 months, melanocyte stem cells have ample opportunity to move back and forth between the hair germ and bulge region throughout one’s lifespan. With each hair cycle, however, fewer cells return to the hair germ. In fact, Sun et al. reported that initially 85% of melanocyte stem cells that traveled to the bulge region returned. When these hairs were then plucked from the mice and forced to age, only 50% made it back. The remaining seemed to get stuck in the hair bulge, where they were no longer able to mature into melanocytes and generate hair color. Less melanocyte stem cells available in the hair germ may be what leads to graying hair.
If these cells can get “stuck”, there may be a way to get them “unstuck.” Although environmental and lifestyle factors also influence aging, people that report gray hairs earlier in life may have fewer melanocyte stem cells to begin with. Thanks to Sun et al. we are one step closer to not only preventing but also reversing gray hair.