Sirtuin expression in skin fibroblasts: pharmacomodulatory effect of quercetin

Introduction. Sirtuins (SIRTs) are NAD+-dependent histone deacetylases involved in the intracellular regulation of multiple biological processes including DNA repair, autophagy, inflammation, oxidative stress defence and metabolism associated with age-associated diseases, including dermal ageing. Reduced levels of these proteins in tissues correlate with the progression of endothelial dysfunction and cellular aging, which makes sirtuins promising targets for the prevention and therapy of age-related pathologies. The development of strategies to activate the expression of SIRT -1, -3, -6 in cells to inhibit the aging process is relevant. The natural flavonoid quercetin, a natural flavonoid with proven geroprotective efficacy, is capable of influencing sirtuin gene expression. Purpose. To study the modulatory effect of quercetin in the hyaluronan gel on the content of endogenous geroprotective proteins SIRT -1, -3, -6 in human skin fibroblast culture during the development of inflammaging. Material and methods. The study was carried out on cell cultures of human skin fibroblasts with modelling of genotoxic stress inflammaging by UV-irradiation. 1 ml of hydrogel preparation with quercetin was injected into growth cultures, obtaining 3 groups of cells under study. Methods of immunocytochemistry and immunofluorescence confocal microscopy were applied to visualise the content of sirtuins in them. The obtained images were analysed using ImageJ software. Relative area of expression was calculated as the area of marker expression to the total area of the field of view. Statistical processing was performed in Origin. Results. Revitalisant containing hyaluronan and quercetin showed effective enhancement of SIRT-1, -3, -6 levels in senescent skin cells. Conclusion. Quercetin, an activator of SIRT-1, -3, -6 dermal anti-aging biomarkers, has therapeutic potential in the treatment of age-related pathologies. Selective pharmacological modulation of sirtuin activity in skin fibroblasts by quercetin appears to be an effective and promising way to slow down dermal aging.