An Improved Human 3D Skin Model for Aging Research

Current models used to study skin aging, including in vivo murine models, ex vivo human skin, and in vitro 2D cell cultures, present significant limitations in replicating the complexity of chronological human skin aging. To address this gap, we developed a novel 3D human full-thickness skin aging model using primary dermal fibroblasts and epidermal keratinocytes harvested from the same aged donors (average age 80 years). Comprehensive histological, immunostaining, and transcriptomic analyses of this aging model, compared to a young 3D skin model (average age 20 years), revealed distinct hallmarks of chronological skin aging, including reduced epidermal and dermal thickness, decreased extracellular matrix content, diminished cell proliferation, and increased cellular senescence. Furthermore, 3D aging skin model also showed reduced IGF-1 expression and induction of AP1/JunB, which were consistent with observations in aged human skin. Transcriptomic profiling further identified upregulated pathways associated with extracellular matrix degradation, cellular senescence, and immune responses, aligning closely with published data from human aged skin. This novel in vitro model faithfully recapitulates several key features of chronological skin aging, offering a robust platform for studying aging mechanisms and testing therapeutic interventions. We have used microarray to study the gene expression profile of 3D skin models Total RNA was isolated from 3D skin models at day 14 and day 21 of culture and used for microarray