# Decreased S100A7 expression is linked to altered differentiation-, autophagy- and senescence-related programs during skin aging

## TL;DR

The study shows that lower levels of S100A7, an antimicrobial peptide, are linked to changes in skin aging related to cell differentiation, autophagy, and senescence.

## Contribution

The novel contribution is identifying S100A7 as a modulator of epidermal homeostasis and establishing a new AMP–autophagy axis in skin aging.

## Key findings

- S100A7 depletion alters differentiation-, autophagy-, and senescence-associated pathways in aged keratinocytes.
- S100A7 supplementation increases autophagy and reduces senescence-like phenotypes.
- S100A7 knockdown mimics senescence-associated signatures.

## Abstract

Skin aging involves progressive structural and functional decline, yet the underlying molecular mechanisms remain unclear. Here, we report that the antimicrobial peptide S100A7 is markedly reduced in aged keratinocytes and that its depletion leads to transcriptional alterations in differentiation-, autophagy-, and senescence-associated pathways. S100A7 knockdown partially recapitulated senescence-associated signatures, whereas supplementation increased autophagy and attenuated senescence-like phenotypes. These findings support a role for S100A7 as a context-dependent modulator of epidermal homeostasis and establish an AMP–autophagy axis that may contribute to cellular changes during skin aging.