[Signaling molecules and skin aging: Targeted prevention approaches in molecular cosmetology.]

Abstract

Chronic genotoxic stress leads to the development of inflammaging in human skin fibroblasts, a condition characterized by the accumulation of DNA damage, overexpression of pro-inflammatory factors, and degradation of the extracellular matrix, which makes it important to find ways to correct these processes. Hydrogel preparations based on hyaluronic acid with chelated forms of micronutrients are considered promising. Therefore, the aim of this study was to investigate the effect of a hyaluronic acid-based hydrogel with a chelated form of zinc and silicon on the expression of cellular aging biomarkers CCN1, IL-8, Ki-67, MMP-3, NF-κB/p65, and TIMP1 in human skin fibroblast cultures under genotoxic stress. Inflammaging modeling was performed on human dermal fibroblasts by exposure, causing a critical threshold of damage to chromosomal DNA. In the experimental samples, a preparation based on hyaluronic acid with a chelated form of zinc and silicon was added to the culture, after which the expression of these biomarkers was evaluated. The results showed that genotoxic stress in this model activates the degradation of extracellular matrix proteins and causes a sharp increase in the expression of IL-8, CCN1, and NF-κB. In all the samples studied, the addition of the preparation to a culture of fibroblasts exposed to genotoxic stress resulted in a significant restoration of the proliferative (associated with Ki-67) and biosynthetic functions of dermal fibroblasts, as well as a decrease in key markers of inflammaging. Thus, a hyaluronic acid-based preparation with a chelated form of zinc and silicon effectively corrects the molecular signs of cellular aging and the inflammatory phenotype under genotoxic stress, which justifies its potential use for the prevention and correction of age-related skin changes.