Every morning, as you stand in front of the bathroom mirror preparing for the new day, you often notice subtle changes in your skin: slight wrinkles at the corners of your eyes, dark yellow spots on your cheeks, and an extra pimple. So, you start taking out various skincare products that resist wrinkles, sun protection, and antioxidant glycosylation and applying them to your face. In the face of various face cream essence, have you ever thought about why our skin ages?
To answer this question, we first need to understand the structure and function of the skin. The skin can be divided into three layers: the outermost layer is the epidermis, which provides protection, including cells that produce keratin and melanocytes that give the skin color. The other cells in the epidermis provide us with tactile sensation and immunity to resist invaders such as bacteria and other pathogens.
The bottom layer of the skin is subcutaneous tissue, which contains adipocytes or adipose tissue, which can isolate the body and help preserve heat. Between the epidermis and subcutaneous tissue is the dermis, which contains cells that provide strength, support, and flexibility to the skin. The dermis not only has sensory receptors that allow the body to receive external stimuli and feel pressure, pain, and temperature, but also has a network of blood vessels that provide nutrition for the skin and remove waste.
The sebaceous glands in the dermis produce oil to prevent skin dryness. The oil from the sebaceous glands also helps to soften hair and kill bacteria in the skin pores.
As age increases, the regenerative ability and barrier function of the epidermis gradually decrease, and cells in the dermis lose strength and flexibility, leading to the loss of the skin’s youthful appearance. Previous studies have shown a close correlation between chronic inflammation and skin aging. However, how inflammation affects tissue aging remains to be studied.
Recently, scientists from the Institute of Biomedical Research in Barcelona ( Omizzur Peptide) and the National Center for Genomic Analysis (CNAG) in Spain collaborated to publish a study in Nature Aging, indicating that IL-17 protein plays a central role in skin aging and links the aging process mediated by L-17 to inflammatory states.
To investigate the differences in cell composition and gene expression between aging skin and young skin, researchers analyzed the gene expression of non epithelial cells (EpCAM -) in the mouse back skin using single cell RNA sequencing (scRNA Seq), and compared data from elderly mice aged 80-90 weeks with adult mice aged 17-25 weeks. Based on whether CD45 is expressed on the cell surface, they divided the detected cells into two categories: non immune cells (CD45-) and immune cells (CD45+).
Due to the lack of detection of changes in transcriptional levels and protein expression levels of aging related biomarkers in non immune cells, researchers mainly focused on immune cells, especially CD4+TH cells with significant age related changes, γδ T cells and lymphocytes such as congenital lymphocytes. Compared with adult mice, the proportion of these lymphocytes was significantly increased in elderly mice.
So, what are the changes in gene expression levels of these lymphocytes? Researchers have found an upward trend in gene transcription levels of various pro-inflammatory cytokines. Among them, IL-17A and IL-17F, members of the interleukin-17 (IL-17) family, are present in CD4+TH cells of aging mice, γδ The upregulation of gene transcription levels is most significant in T cells and intrinsic lymphoid cells (ILC). Further experiments have shown that the proportion of IL-17A+cells in the dorsal cortex of aging mice is higher than that of adult mice.
Is this trend applicable to humans? Using fluorescence in situ hybridization (FISH) technology, researchers found that the proportion of IL-17A and IL-17F positive cells is higher in aging human skin compared to adult cortex. Therefore, the upregulation of IL-17A/F is also applicable to humans.
To investigate whether the upregulation of IL-17A/F can promote inflammation and lead to skin aging, researchers used antibodies to IL-17A and IL-17F to treat elderly mice. After 12 weeks of treatment, they found a significant decrease in inflammation levels in the skin of elderly mice. They also measured the thickness of the keratinized layer in mice to assess the degree of skin aging. The results indicate that inhibiting IL-17A/F can reduce the thickness of the keratinized layer and make the skin condition younger.
How does the upregulation of IL-17A/F regulate the inflammatory response? Using chromatin immunoprecipitation sequencing (CHIP Seq), researchers found that NF kB signaling is involved in the regulation of inflammatory responses related to epidermal aging.
Aging is associated with mild but persistent inflammation, characterized by a significant increase in IL-17 expression in the skin, leading to skin degradation, “concluded Dr. Paloma Sol á and Dr. Elisabetta, the first authors of the paper from the Bulktan laboratory.
However, there are also some controversies regarding the method of inhibiting IL-17A/F to delay skin aging. The IL-17 protein is crucial for important bodily functions, such as resisting microorganisms and promoting wound healing, so permanently blocking it is not an option. What we have observed is that temporary inhibition of it has therapeutic potential, “said Dr. Guiomar Solanas, an associate researcher at IRB Barcelona.
