Long-term human skin platform models chronic inflammation and senolytic treatments

In human skin tissue samples from 20 donors, researchers established an ex vivo platform that preserved native architecture and transcriptional programs for up to four weeks. Time-course RNA sequencing across 199 samples revealed an initial culture adaptation phase followed by stable tissue-associated gene expression. Sustained stimulation with IL-17 and IL-22 for three weeks drove chronic inflammatory programs, structural deterioration, and secretion of IL-8, MCP-1, S100A8/A9, and MMP-1. Tofacitinib, a Janus kinase inhibitor, broadly suppressed these changes. In aged donor tissue, prolonged senolytic-associated treatment reduced inflammatory signaling, remodeling pathways, and secreted factors such as IL-6 and MMP-1, with significant effects appearing at week three but not week one. Ultraviolet B exposure also triggered inflammatory responses that topical sunscreen prevented.