Enhancing effect of polyoxometalates on the aging stress responses of skin cells

Abstract

The accumulation of senescent cells has attracted attention as a cause of aging. Various environmental factors have a harmful effect on the skin, causing aging stress in skin cells, which in turn promotes cellular aging through the accumulation of reactive oxygen species. Stem cell-secreted exosomes also play important roles in skin regeneration and stress relief. Among the polyoxometalates with various biological activities, VB1: vanadyl sulfate (VOSO4), VB2: K11H[(VO)3(SbW9O33)2]・27H2O and VB3: Na2[SbW9O34]・19H2O have been developed as cosmetic ingredients that can be applied to the skin. We evaluated whether these VBs could enhance the resistance of cells to skin aging stress and examined the underlying mechanisms. In this experiment, skin fibroblasts were subjected to glycation (advanced glycosylated end products), oxidation (hydrogen peroxide), and photoaging (ultraviolet irradiation for 5 or 25 min), and VBs were applied before or after treatment. Whether VBs enhance the cellular stress response was determined by changes in the mRNA levels of three parameters (collagen, elastin, and hyaluronic acid synthase). We also investigated whether treating stem cells with VBs results in the secretion of exosomes with properties different from those normally secreted. In addition, because intracellular reactive oxygen species accumulation was suppressed in human dermal fibroblasts treated with VBs, as shown here and in our previous study, the mitochondrial oxygen consumption rate and uptake of cystine, a raw material for the synthesis of the intracellular antioxidant glutathione, were also examined. According to the results of those experiments, we concluded that VBs could enhance stress responses to all the aging stress examined. Vanadyl sulfate likely showed direct effects on dermal fibroblasts, while VB3 was supposed to exhibit the effect via modification of exosomes secreted from mesenchymal stem cells. In addition, VB2 might be involved in the stress response through both direct action on the cells and by inducing the production of exosomes suitable for the stress response. It has been suggested that a combination of several types of VB may exert multifaceted anti-aging effects.