 We've done a series of videos on what biologists call the hallmarks of aging, things like cellular senescence, mitochondrial dysfunction, and genomic instability. But those aren't the things most people think of when you mention aging. If you ask a random person what the hallmarks of aging are, you'll probably get a list of things like wrinkled skin, bad joints, and gray hair. So, what can biology tell us about those more familiar features of aging? Welcome to X10, your one-stop YouTube show for all things life extension. Learn the science, keep up with new research, and live longer and healthier. If you're new here, you can subscribe to hear about new videos and press the bell icon and select all notifications so you won't miss a thing. In this episode, we'll talk about hair going gray. A paper that dug into the hows and whys of the process turned up some unexpected results. Let's start with a closer look at a single hair. Each hair grows from a follicle, which is an organ made up of different types of cells that support and regulate hair growth. We don't need to go into all of the different cell types. The important thing is that cells known as melanocytes inject melanin pigments into the growing hair, giving it color. You get gray hair, well, actually white hair, when the melanocytes stop doing their job. Why that happens is still a bit of a mystery. The dominant idea is that the stem cells that produce melanocytes eventually stop working, perhaps due to hormonal changes or because of accumulated damage or other factors. There is also the common sense notion that graying hair is somehow a result of stress, but it's not really clear what the link is. And then there's variability in when people get gray hairs. You've probably noticed that some people already start to go gray in their 20s, or even earlier, while others have hardly any gray hair in their 50s or 60s. So how does all of that come together? What did the researchers do in the new study, and what did they find? The first thing they had to do was get sensitive and precise measurements of the pigmentation of human hairs. They plucked around 400 hairs in total from 14 people and took standardized images of them using a digital camera, a high-quality scanner, and an electron microscope. That gave them a detailed picture of different pigmentation patterns. It also let them see that the melanocytes in white hairs have fewer and smaller pigment-carrying organelles. The really interesting discovery was that hair graying seems to be reversible. They found several cases in which a hair had lost its pigmentation and then regained it. If a gray hair can regain its pigment, then graying probably isn't because the melanocytes are damaged beyond repair or can't be replaced. That might be why some hairs go gray, but in other cases, there must be a reversible process at play. That idea is in keeping with the results of the proteomic analysis done in this study. The researchers found that white and pigmented hairs had different protein profiles and the differences point towards changes in their cellular metabolism. The other really cool thing that they found was that different scalp hairs lose their color at the same time. That means that graying is probably regulated by systemic factors rather than being a unique process for each hair follicle. This data put the researchers into a position to check whether stress actually affects hair color. They could use the growth of a single hair as a record of the past, similar to tree rings, and then see if changes in pigmentation matched with periods of increased stress. That's exactly what they found. For example, a woman had a hair that went completely gray and then completely reversed. The growth analysis pointed to a two-month window of graying that matched strikingly well with her report of two months of major stress from marital conflict separation and relocation. Putting all this together, the researchers propose a model in which graying happens because of the accumulation of an aging factor and a stress factor. When these factors go over a follicle's threshold, it stops putting pigment in the growing hair. But the process can be reversed if, for example, stress levels drop again. Working out what the different factors are and how they're controlled might help us figure out how to delay, stop, or even reverse the process. In the meantime, the ability to use hair pigmentation as a proxy for stress or other life history events will probably prove a useful tool for researchers in a range of fields. Of course, this isn't the only research that's been done on gray hair. For example, a 2018 paper comes at the topic from a very different angle. The researchers were curious about an unexpected interaction between two genes that they introduced into lab mice. One of the genes, MITF, is an important genetic regulator in melanocyte stem cells and melanocytes. Their analysis revealed that several genes involved in the innate immune response are regulated by MITF. The gene expression patterns in cells with only one active copy of MITF was characteristic of viral infection or autoimmune disorders. The researchers built on those results to show that a mock viral infection could cause mice to get gray hairs if they were overexpressing SOX10, the other gene in their study. The takeaway here isn't the details of those interactions. It's that research into how and why hair turns gray has uncovered a stem cell development gene that also regulates immune response. It's that learning about even seemingly unimportant biological processes can help us piece together how the ridiculously complex systems known as organisms work, how they age, and what we might be able to do about it. Thanks for watching. Please click the like button if you enjoyed it and don't forget to subscribe if you'd like to know when we release new videos. You can also leave a comment below to tell us what you liked about the episode or how we could do better. This episode and all of our work at X10 is made possible by the Lifespan Heroes. If you'd like to help promote and support longevity research, go to lifespan.io slash hero and make a pledge.