[Molecular mechanisms of the geroprotective effect of exosomes in the simulation of inflammaging in the culture of human fibroblasts.]

Abstract

Inflammaging is considered as a fundamental mechanism of age-related skin involution, mediated by chronic inflammation, fibroblast dysfunction and collagen matrix degradation. The study considers the modulating effect of exosomes on the culture of dermal fibroblasts (DF1) during inflammaging. The experimental model included three groups: intact control, induced inflammaging, inflammaging in the presence of exosomes. The methodology was based on an MTT test to assess the metabolic activity of cells and immunohistochemical analysis with detection of a panel of markers involved in the regulation of inflammation (NF-κB/p65, CCN1), redox homeostasis (superoxide dismutase, prohibitin), cell cycle (p53, Ki-67), as well as endogenous geroprotective factors (Klotho, SIRT6) and receptor apparatus (EGFR). It has been shown that exosomes initiate a multiple cytoprotective response. At the same time, endogenous antioxidant systems are activated (the expression of Klotho and prohibitin increases), which is accompanied by an increase in the activity of superoxide dismutase and a reduction in oxidative stress. There is also suppression of stress-induced signaling cascades - inhibition of p53 correlates with the preservation of the proliferative potential of fibroblasts, while suppression of transduction along the NF-κB/CCN1 axis reduces the pro-inflammatory load and stabilizes the extracellular matrix. Thus, the results of the study indicate that exosomes, acting on the key pathogenetic links of cell aging, can be considered as potential geroprotectors.