BACKGROUND: While human skin aging involves complex transcriptional alterations, the cell-type-specific regulatory mechanisms and therapeutic targets remain incompletely defined. The study aims to investigate aging-associated transcriptional programs and drug-responsive signatures at single-cell resolution.
METHOD: Here we performed a single-cell RNA sequencing of young and elder human skin cells and provided a comprehensive analysis of aging-related genes, a gene regulatory network with immunohistochemistry (IHC) validation, cell-cell interference as well as potential chemical reactions.
RESULT: Total 10 distinct cell populations were analyzed based on the scRNA sequencing data. Gene regulatory network analysis showed decreased lactotransferrin gene expression and increased FOSB(+) and DDIT3(+) regulons' regulatory activity. IHC identified the FOSB as an aging-related transcription factor. Despite uniform MT1 protein distribution across epidermal layers, single-cell data revealed subcluster-specific MT1 mRNA dynamics linked to metal ion homeostasis. Drug response prediction experiments revealed possible drug targets and potential antiaging drugs for the skin.
CONCLUSION: Our data showed the skin cell clusters presented distinct transcriptional signatures during skin aging. We highlighted the versatile expression profiles of metallothionein family genes and identified the aging-related signature FOSB in the aged skin. We also provided potential target resources for antiaging therapies.
