Aging rewires skin cells to amplify inflammation in aged mice

When skin ages, its outer layer has a harder job: it must still regenerate, close wounds and maintain a barrier, even as persistent inflammation builds. In experiments led by Guiomar Solanas in Barcelona and Salvador Aznar Benitah at IRB Barcelona, researchers traced that inflammation to a change in how two proteins operate inside epidermal cells. BMAL1 and YAP began helping activate inflammatory genes.

The two proteins normally have useful jobs. BMAL1 belongs to the circadian clock, which coordinates processes across the day; YAP helps cells adapt to physical changes in their surroundings. In adult epidermis, their cooperation supports the identity and function of skin cells. With aging, changes in skin stiffness and increased inflammatory signals concentrate both proteins near DNA regions that control inflammation.

The mechanism completes a chain that the same laboratory began mapping in 2023, when it identified IL-17 as a key signal in skin aging. IL-17 comes from immune cells in the dermis, the deeper skin layer. The new study found that the signal helps activate YAP inside epidermal cells, which then increases activity linked to inflammatory genes.

In aged mice, blocking IL-17 reduced YAP-associated activity and lowered expression of the inflammatory genes examined. That result gives researchers a more specific place to investigate than inflammation alone: the handoff between an immune signal and the skin cells that amplify it. The study was published in Nature Aging, with researchers from the Max Planck Institute for Molecular Biomedicine in Münster also participating.

So what changes in practice? Not a treatment yet. The work clarifies a mechanism that researchers can investigate, but the team’s next step is to determine whether it can be regulated safely without disrupting essential epidermal functions. The evidence comes from experiments, including aged mice, and no safe human intervention is reported.