UAB research that aims to eliminate gray hair, and then old age

Gray people, time passes for everyone! But from today it could go back and at least restore your hair color. UAB research explores ways to "rejuvenate" gray hair.

The search for Melissa harris indicates a new paradigm for identifying and reversing the process that makes hair gray. "It was thought that once the hair went gray, all stem cells were lost. With no chance of return," he said. Harris, "but presumably they can be reactivated".

Molecular biology is not the kind of science you can do with the naked eye.

Melissa Harris, Ph.D., runs a lab that relies on CRISPR gene editing tools, single cell sequencing studies, and analysis algorithms. But all she needs is a look to diagnose the status of melanocyte stem cells, and evaluate their effect on gray hair.

This is the beauty of gray hair as a model for aging: if your hair is all one color, the stem cells for your hair are fine. Wherever there is gray hair mixed, however, something has gone wrong.

You are getting older? It's a possibility. Is this an inevitable thing in the aging process? It is no longer so. It is no longer said.

Harris, who is also an assistant professor in the Department of Biology, has spent the past decade uncovering the relationship between stem cells and baldness. Most importantly, however, he looked for evidence that age isn't the only reason melanocyte stem cells fail.

He is now focusing his research with mice on a new task: to demonstrate that there may be a way to bring those cells (and their original colored pigments) back from the dead.

Harris' lab is working with a biotechnology startup to study an experimental compound that appears to restore long-term hair color in mice.

Why does the hair turn gray?

Hair color comes from melanocyte stem cells, which live near the root of each of the approximately 150.000 bulbs we have on our heads. (That is, if you have an average amount of hair, otherwise the search for you is this other one).

Each hair survives approximately seven years. When it falls, a new one begins to grow in its place. This is the signal for some of the stem cells waiting for the melanocytes that wake up, transform (differentiate) into melanocyte cells that produce pigments and migrate to the hair root, where they inject pigment into the hair shaft as new hair grow.

Researchers suspected that, with age, melanocyte stem cells all differentiated into melanocytes, or otherwise disappeared, leaving no stem cells as a reserve to form a new group of melanocytes.

Melissa Harris has been working on the problem for the past ten years and has discovered a much more complex picture.

She and her lab team identified several causes of graying hair, and encouraging evidence that melanocyte stem cells can also survive when hair turns gray. They may be in a state of deep sleep and the right signal may wake them up.

Goodbye tinctures, but not only

Recoloring hair is not Harris's ultimate goal. His work has applications on many pigment disorders such as vitiligo or even melanoma which is cancer of melanocyte cells.

The ultimate goal is to understand why somatic stem cells (found in muscles, bones and organs throughout the body and are crucial. For tissue regeneration, immune defense, wound healing and EVEN the color of hair) give out as we age.

"To treat or prevent aging, we need to be more specific, we will need personalized therapies based on single genetic or molecular factors," said the scientist. To do this it will be important to understand the mechanisms that interrupt the life cycles of stem cells.

Most of these stem cells are notoriously difficult to work in the laboratory: it is not easy to manipulate their genes without catastrophic results. But melanocyte stem cells are an exception.

Science of vanity

"Everyone has gray hair", said Harris. But research on this topic has a bad reputation "It is considered the science of vanity", He says. As you like to point out during your speeches, however, "I'm not a vain person. My lab has chosen the most appropriate model to investigate what happens to stem cells as we age."

The work earned her a prestigious K99 / R00 Pathway to Independence fellowship from the NIH's National Institute of Aging, and some fame in the field of aging research. Colleagues call her "the gray-haired lady".

Gray hair? I am in your destiny

Graying of hair is inevitable. "Between 61 and 65, 91% of people have some level of graying of their hair"Says Melissa harris. But some people have far less gray hair than others, he continued. Because? One of the factors we know how to contribute is the genetic background.

A 2012 study in France indicated the presence of gray hair in people aged 45 to 62 of various origins. The "continental" French had the highest probability of being gray in that age group: 93%. At the opposite end of the scale were Frenchmen of sub-Saharan origin; only 43% of them had gray hair. As these numbers suggest, there is significant variability: what changed in 7% of "continental" ones, or in 57% of "sub-Saharan" ones who still had their original hair color?

An infection might be enough

"Perhaps, in an individual who is healthy but predisposed to gray hair a simple daily viral infection is enough to cause melanocytes to decline, leading to premature gray hair, "Harris says. It's not yet a fully studied mechanism in humans, but it would explain several cases.

"Colored" regrowth, a compound that amazes

Harris received a contact from a small biotech startup last year. They had an experimental compound in development to regrow hair, and it seemed to affect pigmentation as well. The company wanted to understand more about the mechanism, and asked Harris to test the compound in the laboratory.

"I was skeptical", said Harris. "But I agreed to do some research. And it looks great. When I gave the compound to the mice, I saw hair repigmentation. The mice lose their hair, the hair grows back and maintains the highest level of pigmentation, suggesting that the process is permanent ".

This compound is reprogramming the stem cells, bringing them to a younger state, allowing them to start over.

Harris and one of his graduate students, Joseph palmer, they suspect that melanocyte stem cells could be affected by a phenomenon called the "quiescent program". Stem cells from melanocytes, for example, are only called into question every seven years or so when new hair grows. They spend the rest of their time in a form of hibernation, and perhaps with age it just becomes harder to wake them up.

PD-L1 protein and its role in gray hair

Spanish doctors wrote in the journal JAMA Dermatology to have noticed a strange side effect in more than a dozen patients undergoing immunotherapy for lung cancer: hair repigmentation. PD-L1 is a protein that suppresses the immune system: blocking it allows a vigorous immune response against cancer cells.

Harris' lab examined the quiescent stem cells of the melanocytes and found that expressed more PD-L1 proteins than actively dividing cells. "And as you progress into quiescence, the cells express more PD-L1 and are harder to reactivate. We need to give them a good wake up call," says Harris.

Research has convinced the scientist that a new paradigm is at stake.

The canonical pathway (progressive loss of melanocyte stem cells and graying of hair) gives way to a new paradigm of "sleep" of melanocyte stem cells, which makes the hair gray. This suggests that we can find therapies to reactivate them. The compound being studied could be a very, very promising path.

"We have the opportunity to find out what are the potential ways we can fix a failed system", Harris said. "We are always looking for what is broken, we rarely go in the opposite direction, towards tissue rejuvenation. This is why it is a study that excites me."

The prospect of reactivating our cells by stopping the gray color of the hair and making it grow back, and then perhaps reversing old age itself is not bad, in fact.