:max_bytes(150000):strip_icc()/internal-shingles-risks-and-complications-5180098-FINAL-1bb25788aa7042c78689986b69df5f96.jpg "What causes our skin to age? Inflammation, possible suspicion")
When we are young, wounds or scratches heal within days; the skin thickens and regenerates easily. But as we age, our skin loses its elasticity and thins, weakening its ability to repair itself. Now researchers at the Barcelona Institute of Science and Technology have identified a key mechanism behind the aging process: a signaling protein called interleukin-17 (IL-17). Published in the journal Nature Aging , a discovery from Salvador Aznar Benita's lab offers an exciting new way to try to slow down or even prevent skin aging.
The skin. The first line of defense
Our skin consists of three layers: epidermis, dermis, and hypodermis. The epidermis is the outermost layer that provides the first line of defense against damage and infection. This is the skin you see when you look at your hands or feet. It is a physical barrier that helps prevent unwanted access. Then you have the dermis, which is the second layer. It contains connective tissue, hair follicles, blood vessels, lymph vessels, and sweat glands. Finally, the hypodermis is the deepest layer, consisting mainly of fat and more connective tissue.
In addition to physical protection, the skin also acts as a barrier for our immune system. Because anything that penetrates the skin carries the risk of infection, the skin is filled with a variety of immune cells, including macrophages, monocytes, B cells, and T cells. These cells are activated at the slightest sign of damage or infection. . come together to form a complex defense network.
Salvador Aznar Benita and his colleagues were particularly interested in changes in the skin's immune cells; do their numbers decrease with age? Have they become less active? What is happening?
How does the skin change with age?
To answer this question, the research team turned to a laboratory technique called single-cell RNA sequencing. This technique allows thousands of individual cells to be analyzed at once. Think of it as a snapshot of a particular room at a particular time. These photos contain important information about cell composition and activity. Comparing images of cells at different stages of the aging process can provide valuable clues about how cells change over time.
The scientists took skin cells from old mice (80 to 90 weeks old) and compared them to young mice (17 to 25 weeks old).
First, they looked at non-immune skin cells. To their surprise, there was not much difference between the two groups. aside from a very subtle increase in overall inflammation, the skin cells of young and old mice were very similar.
The scientists then analyzed the skin's immune cells. Here they saw a clear gap between the two age groups. The myeloid immune cell line (part of our innate immune response) is significantly more active in aging skin. These cells play an important role in regulating inflammation as part of the primary immune response. However, in aging skin, they are activated even in the absence of external threats, leading to chronic inflammation.
A line of lymphoid immune cells associated with the learning or adaptive immune system is also hyperactive. This is particularly seen in CD4+ helper T cells, gamma-delta T cells, and innate lymphoid cells (ILCs). Normally, these cells are found in the dermis and act as sentinels, looking for tissue damage or external threats. During infection, they help coordinate immune defenses and regulate inflammation by secreting pro-inflammatory proteins. Like the myeloid lineage, these cells were more abundant in the skin of old mice and were much more active even in the absence of obvious damage or microbial threat.
IL-17. A known criminal
Inflammation in aging skin is triggered by the interleukin-17 (IL-17) family of signaling proteins. The interleukin 17 family consists of six different members (IL-17A-F). When all is well, this protein mobilizes the immune system to help control inflammation and direct immune cells to where they need to be. But excessive inflammation can be dangerous. This is a double-edged sword. inflammation occurs because it creates a harmful environment that makes it difficult for invading pathogens to survive. However, if left unchecked, this damage will begin to affect healthy tissues and organs. Friendly fire started.
CD4+ helper T cells, gamma-delta T cells, and innate lymphoid cells in the skin of aged mice secrete IL-17A and IL-17F, which induce systemic inflammation. IL-17A is the most studied of the interleukin family and is often referred to as IL-17. Indeed, interleukin 17A is known to be a factor associated with many autoimmune inflammatory diseases, especially of the skin, such as psoriasis. Therefore, the association between skin aging and IL-17 hyperactivity is not unexpected.
Rejuvenates old skin
To confirm the role of IL-17 in skin aging, the researchers treated 75-week-old mice with antibodies that target and block IL-17A and IL-17F. These antibodies are given for 12 weeks. After the treatment, the scientists took samples of skin cells and compared them to an age group that did not receive the antibody.
IL-17 blockade significantly reduced markers associated with skin aging; Genes associated with inflammation were down-regulated, and conversely, the expression of genes associated with healthy wound healing increased. These changes at the genetic level are accompanied by gradual aging of the skin. Compared to the control group, the treated mice had significantly shorter skin, greater regenerative capacity, greater hair follicle growth, and better barrier function.
Food to take home
As we age, the skin weakens (loses its protective function), making it more susceptible to injury, infection, and dehydration. In addition, aging skin has less ability to repair itself when damaged. Through their research, Salvador Aznar Benita and colleagues have shown that widespread inflammation caused by high levels of IL-17 is responsible for these problems. Their work opens up new and exciting ways to slow and perhaps even reverse skin aging. Currently available psoriasis treatments that work by blocking IL-17 could be repurposed for this purpose, possibly helping people with dry skin and wound healing problems.
It should be noted that all these experiments were performed on rats. Although this is common practice, it does not guarantee an accurate understanding of human skin aging; animal models often fail to predict human outcomes in clinical trials. Another important caveat is that while these findings clearly implicate IL-17, it is likely only one piece of a much larger puzzle. The other pieces are still missing.