Nick Lavars, New Atlas, Oct 26, 2021
The role stem cells play in hair loss is one scientists continue to investigate from all kinds of angles, and a new study has uncovered a previously unknown mechanism by which they influence follicle health. The discovery demonstrates how these cells can lose their adhesiveness and become dislodged from hair follicles in aging mice, and also identified genes that could be key to reversing the process.
The study was carried out by scientists at Northwestern University and used live mice as a model for balding in aging humans. The team's experiments involved labeling hair follicle cells, including stem cells, with green fluorescent proteins, which enabled the scientists to observe their activity during aging using a long wavelength laser.
By watching the same hair follicles over many days, they were able to see the entire degradation process play out, which revealed some interesting insights in terms of cellular activity. As hair follicles go through the natural cycle of life and death, a large population of stem cells are thought to remain permanently lodged within them to keep producing hair follicle cells, but the team's investigation showed that some were in fact escaping.
According to the scientists, this is the result of the stem cells losing the adhesiveness that holds them in place, enabling them to escape from their home, called the bulge, and into the dermis, the layer of skin beneath the epidermis. Here, the conditions aren't so hospitable for the wandering stem cells, so most of them don't survive.
"The result is fewer and fewer stem cells in the hair follicle to produce hair," says lead author Rui Yi. "This results in thinning hair and ultimately baldness during aging."
To delve into the reasons behind this phenomenon, the scientists analyzed the gene expression levels within the follicle stem cells in young and older mice, and found levels were lower in the older specimens. They were then able to pinpoint a pair of genes, called FOXC1 and NFATC1, that appeared integral to the process.
Knocking out these genes in the mouse models brought about some interesting results, with rapid hair loss beginning at four months of age, and the mice becoming completely bald within 12 to 16 months. Using live imaging, the team was able to actually capture the individual stem cells escaping.
"We believe this stem cell escape mechanism has never been reported before, because nobody could track the aging process in live animals," Yi says.
Hair follicles were already known to miniaturize as part of the aging process, which scientists have suspected was the result of cells simply dying or not being able to divide as well as we grow older. This novel escape mechanism adds to this body of knowledge around aging and hair loss, and as part of their ongoing research the scientists are now investigating how reinstating the FOXC1 and NFATC1 genes might be able to reverse the process.
"We discovered, at least in part, it is due to hair follicle stem cells migrating away from their niche," Yi says. "Cell death also occurs during our observation. So, our discovery doesn't dispute existing theories but provides a new mechanism."
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