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

The culture platform maintained native tissue architecture for four weeks, revealing treatment effects on aged donor tissue that emerged only after prolonged exposure.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) · Sharma PK et al. · Paper published 29 Sep 2026

Paper

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.

Why it matters

Chronic inflammation and cellular senescence drive progressive tissue dysfunction during aging. This platform provides an intact human tissue system to evaluate how sustained interventions alter age-related remodeling over several weeks.

Caveats

The findings rely on an ex vivo culture system using 20 human donors, which lacks a functional systemic circulation and immune cell recruitment. Whether these prolonged responses directly mirror clinical outcomes in living individuals remains to be determined.

Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.

The paper

Long-Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention

Sharma PK, Schaafsma E, Anderson E et al.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 29 Sep 2026 · Peer-reviewed

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Core geroscience
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