Abstract
The skin is the largest organ in the body to come into contact with solar UV radiation. The UV-A (UVA) spectrum makes up over 95% of solar-UV radiation energy reaching the Earth’s surface and has been recognized as a significant contributor to skin damage. UVA can penetrate beyond the epidermal skin layer into the dermal layer containing fibroblasts. UVA exposure can induce oxidative DNA damage including 8-oxo-G adducts, as well as single-stranded breaks and apurinic -sites believed to accelerate photo-aging. We investigated the protective impact of klotho protein after UVA exposure. Overexpression of the klotho protein was previously shown to extend lifespan in transgenic mice and give them a youthful appearance compared to litter mates. This rejuvenation impact of klotho was demonstrated to be, in-part, due to the protein inducing protective cellular response pathways including principal antioxidants proteins superoxide dismutase and catalase. Using human fibroblast cells, we measure the ability of klotho to reduce endogenous as well as UVA-associated DNA damage. We report that exposure of fibroblast cells to klotho containing serum reduces the amount of measurable endogenous DNA damage when used at the optimal concentration. Further, using a novel high through-put UVA platform we demonstrate that pre-incubation with 1% klotho containing media significantly reduces the amount of oxidative DNA damage that is induced, post-UVA exposure. Future research will evaluate whether klotho containing media is also protective in other skin cell types and more complex 3D models.