To address the challenges in human skin aging research caused by a lack of clinically relevant models, our team has developed a 3D ex vivo model of human skin that mimics intrinsic aging (van Lessen, 2024).

The model can be obtained within just three days of culture in a defined, serum-free medium.

The aging phenotype was analyzed using aging-associated biomarkers at both the epidermal and dermal levels.

• In the epidermis, key changes included a reduction in the number of rete ridges, keratinocyte proliferation, and protein levels of sirtuin-1, MTCO1, and collagen 17A1. Conversely, the DNA damage marker γH2A.X showed an increase.
• In the dermis, levels of type I and III collagen were significantly reduced, while the mRNA levels of markers of (inflamm-)aging, such as MMP-1, -2, -3, -9, IL-6, IL-8, CXCL10, and CDKN1, were upregulated.

The model was validated for efficacy testing, using caffeine as a positive control. Caffeine, a well-known molecule with proven anti-aging properties, successfully reversed the aged phenotype.