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

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.