Establishment of Photo-aging In Vitro by Repetitive UVA Irradiation: Induction of Characteristic Markers of Senescence and its Prevention by PAPLAL with Potent Catalase Activity

Abstract

To understand a role of UVA radiation in photo-aging of the skin, we established a model of photo-aging cells using cultured human dermal fibroblasts. Repeated low dose UVA radiation for 10 consecutive days induced senescence in fibroblasts, characterized with 1) increased level of senescence-associated β-galactosidase, 2) flattened large cell shape, 3) accumulation of reactive oxygen species, 4) yellowish coloration and 5) expression of p16. These were also observed in chronologically aged fibroblasts (doubling times >20), whereas none of these were detected in young cells (doubling times <10). Collectively, we propose that fibroblasts exposed to repetitive UVA radiation may be a good model of aged cells to study the mechanism of aging and photo-aging and further to search for novel agents preventing cellular senescence. In addition, H₂O₂ was produced in the culture medium by a single low dose of UVA irradiation. Further, PAPLAL, a nanoparticle of platinum and palladium having potent catalase-like activity, significantly delayed the onset of H₂O₂-induced cell senescence. The present study strongly indicates that repetitive short term UVA irradiation induces aging of cells possibly via H₂O₂ and may be suppressed by potent anti-H₂O₂ agents.

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