The benefits of competition
The ban on competition between stem cells has aged mouse tails
Polina Loseva, "The Attic"
With age, the reserves of stem cells in the skin are depleted, so it becomes thinner, and wounds heal worse. Scientists from Japan and France have discovered a protein that supports the youthfulness of the skin. Stem cells that have a lot of this protein push out those cells where there is little of it. But over time, most cells lose it, competition stops and the skin ages. By the way, this is the same protein, a mutation in which causes epidermolysis bullosa – the disease of "butterfly children".
Mammalian skin consists of several layers. The deepest one is formed by stem cells, which are located on the basement membrane – a dense cushion of intercellular matter. Stem cells divide regularly, budding their descendants into the upper layers, where they replenish the ranks of "working" skin cells. However, with age, stem cells gradually lose their ability to divide, as a result of which the skin becomes thinner and tightens wounds worse.
In search of the causes of skin aging, researchers from Japan and France drew attention to the protein collagen XVII (COL17A1) – one of the many collagens that make up the intercellular substance. It is responsible for the attachment of stem cells to the basement membrane. Defects in this collagen cause one of the types of epidermolysis bullosa, a severe genetic disease in which the skin literally peels off in layers.
It is known that by old age cells lose collagen XVII. Researchers have suggested that this is due to the same stress that causes cellular aging. And indeed, when they acted on mouse skin cells with ultraviolet light and hydrogen peroxide, the amount of collagen in them greatly decreased.
Then scientists decided to trace what happens to aging cells in the skin of mouse tails. They used model confetti mice, each of whose cells produces a randomly selected glowing protein. On this model, it is convenient to follow the fate of individual stem cells: when they divide, a clone of cells glowing with the same color is formed. It turned out that over time, there are fewer and fewer clones in the skin. Some of them seem to push others out of the layer, and they gradually disappear, having lost their support. At the same time, the winning cells, as a rule, contain collagen XVII, and the losing cells have lost it for some reason. When the researchers specifically turned off the collagen XVII gene in individual cells, they were also quickly displaced from the skin.
Based on the results of experiments, scientists propose the following model of skin aging. Each stem cell divides and forms its own clone. If for some reason (for example, under the influence of stress or a new mutation) one of the cells ages, it loses collagen XVII. After that, it holds onto the basement membrane worse, and healthier cells mechanically squeeze it into the upper layers of the skin. Thus, cellular competition allows the skin to remain young. At the same time, there are gradually fewer clones. And when the winning cells begin to age with age and lose their collagen XVII, there is no one to replace them.
"Attic" has already written about the phenomenon of cellular competition – recently scientists from Portugal suggested that it is useful for removing old cells from the brain in Alzheimer's disease. In the case of mouse skin, it also plays an important role, which turns into trouble in old age. Nevertheless, some stories about cellular competition have a happy ending – for example, sometimes an unexpected improvement occurs in patients with epidermolysis bullosa. This is due to the fact that individual skin stem cells mutate, randomly restore the work of collagen XVII and displace defective cells from the tissue. The phenomenon has been called "natural gene therapy", and together with new research, it confirms our ideas about the importance of cellular competition for the normal functioning of tissues.
Article by Liu et al. Stem cell competition orchestrates skin homeostasis and aging published in the journal Nature.
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