Various Genes That Control Hair Growth

Hair covers the majority of the body and is an important cosmetic feature, especially when it comes to our scalp or beard hair. Hair is constantly growing and shedding, as we all know from our own personal experiences - handfuls of hair in the shower as a woman or the daily need to shave as a man. Every day we lose 50-100 scalp hairs, while every month our scalp hair grows about 1cm.^[1] Each individual hair has a root like a tree called the follicle. The hair follicle accomplishes the cycle of growth through 3 major phases: anagen (growth), catagen (regression), and telogen (rest). A minor fourth phase exists called exogen (shedding).^[2] Each phase is important and determines the fate of a single hair, but how does each follicle know when to move into which phase? The genetic makeup of all follicles is the same, so what is it that makes one hair shed while the other grows? The answer involves epigenetics, the mechanism that controls how DNA is expressed and how the genes that control hair growth become active or inactive.

What Is Epigenetics?

DNA is the building block that contains our hereditary material, or our genetics. Scientists once thought that the sequence of our DNA is the only thing that determines who we are. However, recent researchers have found that our body actually modifies the expression of our DNA. There are 3 major ways our bodies do this: methylation, chromatin modification, and noncoding RNAs.

• Methylation, adding methyl groups, turns genes off and demethylation, removing methyl groups, turns genes on.
• Chromatin is the large package that contains the DNA in each and every cell in the body. Chromatin modification makes the package easier or harder to open, making DNA more or less accessible to be read.
• Noncoding RNAs (nRNAs) are small pieces of DNA that can cover up and hide parts of DNA to turn genes off or make genes more visible, turning them on.

These changes in DNA expression are collectively called epigenetics. The influences that control when and which genes get turned on or off are still under intensive research; however, both external environmental factors and our internal genetic programming play a role in epigenetics.^[3] Here are some of the ways we affect our genes to control hair growth:

Anagen: Hair Growth Through Epigenetics

Anagen is the phase in the hair cycle that lasts the longest and determines how long the hair will stay on the body. Once a hair follicle enters into anagen, its thickness and color are set. And if a hair follicle rushes out of anagen and into catagen, it is sure to be shed soon thereafter. So anagen is the place to stay when it comes to hair health.^[4] Knowing the factors that keep hair in anagen can be very useful because it can help regrow lost hair, like in alopecia, or allow people to grow their hair longer.

Deep in the hair follicle, there are cells called stem cells. Stem cells are cells that have the ability to turn into many different cell types in the body, and they can be programmed to become a specific cell type. The very start of hair growth occurs with anagen. One major way stem cells turn into hair follicle cells is through DNA methylation by an enzyme known as DNMT1.^[5] This enzyme is responsible for turning genes off, which creates a good balance of activated and inactivated genes. One study showed that mice without DNMT1 spent less time in anagen, which means their hair did not grow properly. The mice had thinner hairs, decreased hair length, and decreased amounts of hair throughout their bodies.^[5] Humans also have the DNMT1 enzyme within skin stem cells.^[6] Researchers have found that a loss of DNMT1 caused cells to stop dividing properly.^[6] Both of these studies suggest that DNMT1 is required to keep the hair follicle in the growth phase by turning off genes through methylation.

Stem cells have special proteins called polycomb groups (PcGs), which determine the specific cell type a stem cell will become, like a hair follicle cell. It does this by modifying chromatin that can make genes easier or harder to access. A protein called Jarid2 is necessary for one of the PcGs to function. A mouse study found that deleting Jarid2 made it difficult for hairs to enter the anagen growth phase.^[7] This was due to the lack of chromatin modification by the PcGs and an imbalance in genes turned on and off.^[7] No Jarid2 meant no PcGs, which meant no hair growth.

The Bottom Line for the Hair’s Growth Phase (Anagen)

So, what does this mean for your hair health? If we can find things in our environment that increase our DNMT1 enzyme or increase Jarid2 in our hair cells, then we may be able to find a way to keep our hair growing. Hopefully, more research will test if there are ways to even make some hair start growing again.

Catagen: Regressing via nRNAs

Catagen is the shrinking of the hair follicle after the initial growth phase. This is the beginning of the end for the hair. What does this mean for your hair? It stops growing, the follicle begins to regress, and the hair just sits on your skin.

The progression from growing to regressing includes a significant increase in a specific nRNA named miRNA-22.^[4] miRNA-22 was found to turn off a lot of different genes by binding to sites on the DNA, making the gene too difficult to read. It turned off numerous genes responsible for preventing cell death, effectively turning on the hair follicle’s death switch. Higher miRNA-22 means no more growth and hair follicle shrinking.^[4]

Noncoding RNAs are not all bad. Dicer, an enzyme that makes nRNAs, was found to be essential for normal hair follicle development and growth. In a mouse study without Dicer, hair development was very abnormal. On closer inspection, the hair follicles were abnormal and broken down. This study showed that nRNAs are necessary for normal hair development.^[8] Another study showed that when Dicer was deleted the hair follicle stopped growing and moved into a normal hair regression phase.^[9] These studies suggest that Dicer creates specific nRNAs that are important for maintaining anagen. When Dicer is no longer present, the hair follicle regresses.

Noncoding RNAs can serve both good and bad functions in terms of controlling the genes that control hair growth. They can make DNA easier to read or more difficult to read depending on how they interact with the DNA. It is a delicate balance among the nRNAs in the hair cells that control hair growth function to be in growth, regressing, or resting phase.

The Bottom Line for the Hair’s Transitional Phase (Catagen)

Catagen marks the end of hair growth, so if we can avoid catagen then we can keep growing our hair in anagen. To do this, we need to find things that either decrease miRNA-22 or increase Dicer.

Telogen: Actively Resting

Telogen is the phase following catagen and known as the resting phase. Your hair in telogen continues to just sit on your skin resting, not growing or changing, but you will lose your individual hair very soon after it starts its resting phase.

Although telogen is the resting phase in hair, this does not mean the cells are inactive. Activity must be ongoing to keep the hair follicle in the resting phase. Think about how your body keeps working even when you’re resting! The PcGs in stem cells, which determine the specific cell type a stem cell will become, are also involved in telogen. Unique PcGs work to turn genes off in stem cells through chromatin modification. When the hair is about to enter into a resting state, the stem cells are activated to enter telogen. These special PcGs turn off hair growth by putting methyl groups on the chromatin containing anagen genes, which pushes the hair follicle to the resting phase.^[10,11] Telogen has always been considered a phase without much activity, but researchers are finding that a lot more is going on within the hair follicle than originally thought.

Beta-catenin, another regulator in the hair cycle, is usually found at low levels in the telogen resting phase.^[12,13] When the levels of beta-catenin increase, the beta-catenin moves to the DNA within the cell and binds to genes responsible for cell division and hair follicle development. This forces the hair follicle to exit telogen, shed its current hair, and re-enter the anagen growth phase.^[14]

The Bottom Line for the Hair’s Resting Phase (Telogen)

Telogen, like catagen, pushes the hair closer to its shedding phase. It is no longer growing, just resting, waiting for its day to fall out in the exogen phase. We could prevent telogen by finding ways to decrease the unique PcG proteins that turn off anagen. If our hair has already made it to telogen, we may be able to keep it there and stop it from shedding, creating fuller looking hair. To do this we need to find factors that could keep low levels of or simply decrease beta-catenin to avoid moving into exogen and shedding our hair.

Hair growth is complex and involves a great deal of factors in the hair follicle and the skin cells to make the process run smoothly. Epigenetics impacts every phase involved in hair growth. Researchers are now trying to identify how our own environment impacts the epigenetics and hair growth so that we can use it to our advantage.

Table 1. Genes that Control Hair Growth in the Hair Follicle

Gene modifiers	Anagen (Growth)	Catagen (Regressing)	Telogen (Resting)	Exogen (Shedding)
DNMT1	High	Low	Low	Low
Jarid2	High	Low	Low	Low
miRNA-22	Low	High	High	High
Dicer	High	Low	Low	Low
Beta-catenin	High	Low	Low	High