By our late 30s, most of us have a growing number of gray hairs. They just show up one day, unannounced, and they continue to hang out, usually unwelcomed. Then, they multiply, steadily, inexorably. That little party becomes a larger party, and eventually the party takes over and kicks everyone else out.
Some of us learn how to embrace the graying of our scalps and other body hair. Others, like me, find it pretty annoying.
So far, there are still no therapies available that biologically and reliably turn gray hair back to its normal color. However, there are some interesting possibilities for relevant therapies in the not-too-distant future, and there are some medications that have, anecdotally, re-pigmented hair as an interesting side effect of their primary function.
Could there be other health benefits of mitigating graying hair beyond just vanity?
In this interview, Prof. Melissa Harris and I delve into these topics and more. Prof. Harris is an assistant professor at the University of Alabama, Birmingham (UAB). Her research program focuses on somatic stem cells and aging as well as the biological basis of graying hair.
Prof. Harris has received numerous awards. She was recognized as a winner of the trans-institute, NIH “Three-minute Talk” competition, in which she was challenged to present her work in under three minutes in plain language. She was also the recipient of an NIH Pathway to Independence Award from the National Institute on Aging, a five-year grant for postdocs transitioning to faculty positions. Most recently, she received an NIH High Priority, Short-Term Project Award, also from the National Institute on Aging, to support her studies on therapeutics focused on reactivating old stem cells. Beyond the lab, Dr. Harris teaches undergraduates at UAB the ins and outs of cell biology, histology, and the biology of aging.
We conducted this interview via email.
Why does hair turn gray?
A well-accepted explanation within the scientific literature for why hair turns gray has to do with the loss of a very special stem cell population in your hair follicle. These stem cells are called melanocyte stem cells, and they are specialized to divide and produce the pigment-producing cells known as melanocytes during hair growth. Melanocytes are essentially pigment factories, and, in humans, they make two kinds of pigment, or melanin, that gives each person their unique shade of hair color. The melanocytes have long ‘arms’ called dendrites that deposit the melanin into the hair shaft as it is growing. So, long story short— if you lose melanocyte stem cells, you get no melanocytes, you get no melanin, and thus the growth of a non-pigmented, or ‘gray’ hair. See the attached infographic to help visualize this.
Why have you made studying graying hair and repigmentation a focus of your career?
My research program focuses on stem cells and aging. Stem cells are specialized cells in the adult body that help continually replenish regenerative tissue (like your skin or the lining of your gut) and help provide new cells during tissue injury (like in your muscle tissue). For various reasons, our stem cell populations begin to poop out as we get older, which is one reason you get gray hair! As we just learned with your first question, gray hair is a sign of stem cell dysfunction, and it’s a great visual characteristic to help us learn more about why and what causes stem cells to go awry over time.
Recently, we have also teamed up with biotech companies to tackle stem cell dysfunction from the point-of-view of stem cell rejuvenation. No matter what caused your stem cell dysfunction in the first place, we’d like to see if we can help rejuvenate any of the remaining stem cells to restore more youthful tissue function. Simply, melanocyte stem cells and gray hair are easy to see and easy to manipulate experimentally, making our jobs a bit easier. An added benefit of this model is that gray hair is also very relatable, which makes teaching the public about the value of stem cells super easy and fun!
Do any products commercially available today help mitigate gray hair in a biological/therapeutic way (as opposed to coloring products that simply cover up gray hair)?
As far as I am aware, there are no commercially available products that can be obtained over-the-counter specifically for the purpose of biological hair repigmentation. However, in the scientific literature, you can find examples of clinical case studies where individuals have experienced gray hair reversal after an unrelated therapeutic treatment. One current example of this is a truly remarkable observation made in lung cancer patients receiving PD-1/PD-L1 immunotherapy. See https://pubmed.ncbi.nlm.nih.gov/28700789/
Are any companies developing therapeutics for gray hair based on these “off-label” effects of approved therapeutics for other uses?
I am not aware of a company developing therapeutics for gray hair. However, I believe there is general interest; a recent review highlighted numerous case studies and retrospective studies of medications that result in repigmentation, with the overall and exciting consensus being that gray hair “may not be irreversible.”
What do you recommend as the most viable method for mitigating gray hair at this point?
A really cool, recent study has pinpointed (in mice at least) how stress (from a capsaicin-like compound) can cause gray hair. This paper finally showed the biological link between how we feel and how we look. Of course, this has not been verified in humans, but just looking at past US presidents before and after their presidencies suggests they might be on to something.
Your recent research on MITF and innate immunity in mice has revealed some interesting aspects of the biology of melanocyte stem cells and graying. What are the key results of your research at this point?
In this particular study, what we found was that melanocyte stem cells have a way of dampening their response to factors of the immune system. At least based on our mouse models, it seems that losing this ability is bad for melanocyte stem cells and can cause their depletion. If we extend this idea to humans, what we expect is if an individual has a certain genetic background, their melanocyte stem cells may be more sensitive to activation of the innate immune system (the portion of your immune system that helps protect you against viruses). We haven’t tested this in humans, but it may explain those anecdotal stories about individuals who get gray hair after getting a viral infection. (I caution you, however, to not overinterpret this, as gray hair can be caused in many ways, so gray hair is not an absolute indication of sickness/illness).
While graying hair is annoying for a lot of people (including your interviewer), it’s not high on the list of most people’s major concerns about aging populations and health. Is it accurate, however, to expect that therapies that may truly mitigate gray hair (some stem cell treatments, for example) may have other benefits that extend beyond cosmetic improvements?
Sure! Pigmentation, melanocytes and melanocyte stem cells have been teaching us about important and basic mechanisms in genetics/genomics, developmental biology, and stem cell biology since their discovery. Melanocyte stem cells, like all adult stem cells, share many characteristics with other stem cell populations, and many biological processes important to these stem cells will be relevant for other stem cells. It’s true that not everything about melanocyte stem cells and other stem cells will be identical, simply because there are some features of each stem cell population that make them unique, hence their different functions within the body.
A related question to ask is why melanocyte stem cells are a much better stem cell model than many stem cell populations for studying specific aspects of our biology. For instance, many stem cell populations go into a sort of static state when they are not actively being used, which is called quiescence. Melanocyte stem cells are no exception. But because melanocyte stem cells are located in hairs, which are present on the outside of your body, evaluation of melanocyte stem cells during quiescence is much easier to assess than stem cells that are inside your body. Plucking hairs can be used to easily assess whether melanocyte stem cells are still functioning, and we can very easily determine melanocyte stem cell dysfunction because it is visually apparent in the characteristic of gray hair. Because gray hair is considered cosmetic, the utility of this stem cell population in biological research is often underappreciated.
Is it likely or possible that therapeutics that work for gray hair will also rejuvenate skin more generally? How likely are we to see a hair and skin rejuvenation “package” coming to the market in the next decade or so?
That would certainly be lovely. Interestingly, while the stem cells that support skin tissues and hair follicles work in a coordinated fashion with melanocyte stem cells, aspects of their activation and maintenance are somewhat divergent. This may be because of their developmental origins. So, the short answer is maybe targeting a specific biological pathway will not be enough, but a combination therapy targeting both tissue-specific stem cells simultaneously would be a logical route for a ‘total skin and hair rejuvenation package.’ Another avenue of research that may be promising for broad therapies comes from the biology of aging, and this focuses on slowing aging itself across the body. Caloric restriction, rapamycin, acarbose, reduction of senescent cells, etc. are all showing promise in reducing aging phenotypes across organ systems. However, most of these studies do not evaluate skin/hair/pigment cells! So, the verdict is still out.
What does your latest research show about the ability to repigment gray hair?
Recently, we had the fortune of working with Rivertown Therapeutics, a company that has developed a combination drug that may combat age-related hair loss. Some of its work suggested that this drug is not only good for activating hair growth but might also support hair repigmentation. Using our gray-haired mouse models, we were able to show that topical application of this drug could indeed turn gray mice less gray! You could imagine our excitement to literally ‘see’ that change. Our initial study was published this summer, and we are eager to better understand the key mechanisms by which this drug works, which is what we are focusing on now.
What’s your realistic case estimate of how fast this therapy or something like it will be commercially available for humans? Still 5-10 years away?
“Bench to bedside” has an average timeframe of around 13 years. I’m purely a bench scientist, so it’s hard for me to predict exactly how long commercialization would take; however, with the speed of current research, I remain optimistic and hopeful that we will find effective solutions sooner rather than later.
