Scientists from the Biomedical Research Institute (IRB Barcelona) have developed a work in which they describe a molecular mechanism by which aging modifies the genetic activity of the skin and promotes inflammatory processes, a phenomenon observed in murine models and corroborated with the analysis of data from human skin.
The study, published in the specialized journal "Nature Aging," has been led by Dr. Guiomar Solanas, from the Sant Joan de Déu Research Institute and the Pediatric Cancer Center Barcelona —which was part of IRB Barcelona when the project was carried out—, along with Dr. Salvador Aznar Benitah, a researcher at IRB Barcelona. Its objective has been to unravel why, over time, the skin loses the ability to regenerate, heal, and maintain an effective protective barrier against the environment.
"Among the causes of this deterioration is a mild but persistent inflammation associated with age, but it is still not well understood what mechanisms keep this response active in skin cells," the authors have explained, adding that, during this phase of life, "two proteins, called BMAL1 and YAP, change the way they work together and increase the activity of inflammatory genes in the epidermis, the outermost layer of the skin."
According to Aznar Benitah, the obtained data "show that, during aging, mechanisms that normally maintain the balance of the epidermis change function and begin to amplify inflammation."
In this line, the researchers detail that BMAL1 is part of the circadian clock that regulates numerous physiological processes throughout the day, while YAP participates in the adaptation of cells to the physical changes in their environment. "The study reveals that both proteins collaborate in the epidermis regardless of daily rhythms," they have indicated, later emphasizing that "in adult skin, this collaboration helps preserve the identity and proper function of skin cells."
Connection with a previous finding through IL-17
However, they have specified that "what happens with age is that changes in skin stiffness, along with an increase in inflammatory signals, cause both proteins to concentrate in regions of DNA that control inflammatory genes and increase their activity," while reminding that this advance continues previous work from the same laboratory, published in 2023, in which IL-17 was identified as a key inflammatory signal in skin aging.
In that study, it was verified that, "in mice, the temporary blocking of this protein reduced persistent inflammation and delayed some traits associated with skin aging." In the new research, the authors point out that it delves into what happens "inside epidermal cells when they receive this signal, coming from immune cells in the dermis."
"According to the experiments, IL-17 contributes to the activation of YAP" and when IL-17 is blocked in aged mice, "the activity associated with YAP and the expression of the studied inflammatory genes also decrease," they continued, concluding that "the finding clarifies how aging and inflammation are connected in the skin."