Transcriptome‐Based Evaluation of Hydrogen Gas Effects for Preventing UVA ‐Induced Photoaging Using an Artificial Skin Model

ABSTRACT Aim Intermittent hydrogen gas inhalation has the potential to prevent UVA‐induced photoaging by reducing oxidative stress, although the underlying molecular mechanisms remain unclear. Additionally, alternatives to animal experiments are recommended for studies not primarily focused on pathogenesis. This study aimed to evaluate the preventive effects of hydrogen gas on UVA‐induced photoaging using a short‐term in vitro system with artificial skin. Methods Artificial skin was irradiated with UVA at 0, 7, or 10.5 J/cm 2 /day and incubated for 1 day in a CO 2 incubator with or without 1.3% hydrogen gas. This cycle was repeated three times, followed by one‐day incubation. Transcriptomic and histological analyses were then performed. Results UVA at 7 J/cm 2 /day induced minimal epidermal morphological changes but marked photoaging‐related transcriptomic alterations, whereas 10.5 J/cm 2 /day caused epidermal hypoplasia with excessive apoptosis and only limited transcriptomic changes. In comparisons between the 7 J/cm 2 /day groups with and without hydrogen, hydrogen modulated UVA‐induced biological processes and signaling pathways, including the NRF2‐mediated and the NFκB1–RelA‐mediated responses, and suppressed the p53‐mediated senescence pathway. Conclusions This study demonstrated that photoaging‐related transcriptomic changes were detectable in artificial skin under a relatively low UVA dose (7 J/cm 2 /day; total 21 J/cm 2 ) with minimal histological alterations. Furthermore, hydrogen may have a protective effect against UVA‐induced cellular stress and senescence, via diffusion through the skin surface, suggesting its potential effectiveness in preventing photoaging. This study provides preliminary evidence that may contribute to the development of future translational research on the utility of molecular hydrogen in UVA‐induced photoaging.