Scientists discover why skin becomes less able to repair itself with age

Scientists have identified a mechanism that may explain why aging skin becomes less effective at repairing itself and maintaining its protective barrier. The study found that two proteins — BMAL1 and YAP — change their behavior with age and increase the activity of genes involved in inflammation in epidermal cells.

The research was led by Guiomar Solanas from the Sant Joan de Déu Research Institute and Salvador Aznar Benitah. The findings were published in the scientific journal Nature Aging.

Under normal conditions, BMAL1 is known as one of the components of the body's circadian clock, which regulates numerous biological processes throughout the day. YAP, meanwhile, helps cells respond to mechanical changes in their environment.

The researchers discovered that in the epidermis, these two proteins interact independently of circadian rhythms. In young adults, this interaction helps maintain the normal condition and function of skin cells.

As the skin ages, its properties change. Among other things, it becomes stiffer and produces more inflammatory signals. As a result, BMAL1 and YAP begin to accumulate at regions of DNA that regulate inflammatory genes, increasing their activity.

The role of IL-17 in skin aging

The study also sheds light on the role of the inflammatory protein IL-17. In 2023, the same research group found that this immune signal is one of the key drivers of skin aging. Temporarily blocking IL-17 in mice reduced chronic inflammation and slowed some age-related changes in the skin.

The new study has traced the next step in this process. IL-17, which is produced by immune cells in the deeper layer of the skin known as the dermis, promotes the activation of YAP in epidermal cells.

When researchers blocked IL-17 in older mice, YAP-related activity decreased, along with the expression of the inflammatory genes examined in the study.

The findings therefore describe a mechanism linking age-related changes in the skin with chronic inflammation. IL-17 acts on epidermal cells, where it triggers a YAP- and BMAL1-dependent increase in the activity of inflammatory genes.

According to the authors, the discovery provides a better understanding of why aging skin gradually loses its ability to maintain normal function, repair damage and preserve an effective protective barrier.