Aging reprograms skin genetic activity and promotes inflammation, study reveals

As we age, the skin loses part of its ability to regenerate, heal wounds and maintain an effective barrier against the outside world. Among the causes of this deterioration is low-grade, persistent age-associated inflammation, but the mechanisms that keep this response active in skin cells are not yet well understood.

A study led by Dr. Guiomar Solanas, now at the Institut de Recerca Sant Joan de Déu, Pediatric Cancer Center Barcelona, and Dr. Salvador Aznar Benitah describes a molecular mechanism that explains this process.

During aging, two proteins called BMAL1 and YAP change how they work together and increase the activity of inflammatory genes in the epidermis, the outermost layer of the skin. The work has been published in the journal Nature Aging.

“Our results show that, during aging, mechanisms that normally maintain epidermal homeostasis change function and begin to amplify inflammation,” explains Aznar Benitah, ICREA researcher and head of the Stem Cells and Cancer laboratory at IRB Barcelona.

A machinery that changes function

BMAL1 is known for being part of the circadian clock, which coordinates numerous processes in the body throughout the day. YAP helps cells adapt to physical changes in their environment. The study reveals that both proteins collaborate in the epidermis independently of daily rhythms. In adult skin, this collaboration contributes to preserving the identity and proper function of skin cells.

With age, changes in skin stiffness, together with an increase in inflammatory signals, cause both proteins to concentrate in regions of DNA that control inflammatory genes and increase their activity.

From IL-17 to the skin cell response

The finding builds on a study from the same laboratory, published in 2023. In that work, the team identified IL-17 as a key inflammatory signal in skin aging. In mice, temporary blockade of this protein reduced persistent inflammation and delayed some features associated with skin aging.

The new research shows what happens inside epidermal cells when they receive this signal, which originates from immune cells in the dermis (the deeper layer of the skin). According to the experiments, IL-17 contributes to the activation of YAP. When the team blocked IL-17 in aged mice, YAP-associated activity and the expression of the inflammatory genes studied also decreased.

“In 2023, we identified IL-17 as a key signal in skin aging. Now we have discovered how epidermal cells respond to that signal and amplify inflammation,” explains Júlia Bonjoch, first author of the study.

The finding clarifies how aging and inflammation are connected in the skin. The next step will be to explore whether this mechanism can be safely regulated without compromising essential functions of the epidermis.

Researchers from the Max Planck Institute for Molecular Biomedicine in Münster, Germany, also participated in this study.

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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