# Inflammatory Transformation of Skin Basal Cells as a Key Driver of Cutaneous Aging

## TL;DR

This study explores how skin ages by analyzing cell changes and inflammation, identifying key pathways and genetic factors that could lead to new treatments.

## Contribution

The study reveals inflammatory transformation of basal cells as a novel driver of cutaneous aging through integrated single-cell and GWAS analyses.

## Key findings

- Basal cells can differentiate into inflammatory or spinous cell states during aging.
- IFI27+ keratinocytes increase with age and show heightened inflammatory signals.
- GWAS integration identified key loci linked to antigen processing and oxidative stress in aging skin.

## Abstract

This study comprehensively investigated keratinocyte subpopulation heterogeneity and developmental trajectories during skin aging using single-cell sequencing, transcriptomics, and facial aging-related genome-wide association studies (GWAS) data. We identified three major subpopulations: basal cells (BCs), spinous cells (SCs), and IFI27+ keratinocytes. Single-cell pseudotime analysis revealed that basal cells can differentiate along two distinct paths: toward spinous differentiation or the inflammatory state. With aging, the proportion of IFI27+ cells significantly increased, displaying more active inflammatory and immunomodulatory signals. Through cell–cell communication analysis, we found that the signaling pathways, including NOTCH, PTPR, and PERIOSTIN, exhibited distinct characteristics along different branches. Integration of the GWAS data revealed significant loci on chromosomes 2, 3, 6, and 9 that were spatially correlated with key biological pathways (including antigen processing, oxidative stress, and apoptosis). These findings reveal the complex cellular and molecular mechanisms underlying skin aging, offering potential targets for novel diagnostic approaches and therapeutic interventions.