Senescent dermal fibroblasts: Molecular logistics of the distant and systemic effects of exogenous bioactive compounds in the human body

One of the hallmarks of skin aging is the accumulation of senescent cells, which drives the process of inflammaging. The senescence-associated secretory phenotype (SASP), which characterizes senescent cells, can induce dysfunction in both neighboring skin cells and cells of distant organs. In this study, distant negative effects of senescent dermal fibroblasts on target cells (B-lymphocytes, hepatocytes, and alveolar epithelial cells) were demonstrated. The expression of Klotho, Parkin, SIRT6, VDR, Ki-67, CCN1, p16, and p65 proteins was assessed. The effects of an extract from a plant native to Russia, Hippophae rhamnoides (Sea buckthorn, S), extracts from plants of the African ecosystem Aspalathus linearis (Rooibos, R), Moringa oleifera (Moringa, M), Kigelia Africana (Kigelia, Kg), and an injectable hyaluronic acid gel (HA-gel) on the formation of the senescent phenotype in dermal fibroblasts were evaluated. The studied extracts and HA-gel protected cells from the negative processes induced by genotoxic stress. Moreover, extracts R, S, and HA-gel suppressed the adverse distant effects of damaged fibroblasts, normalizing marker expression in recipient cells, suggesting an influence on signaling pathways involved in the senescent transformation of distant cells. These results suggest considering cosmetic products based on the studied extracts and the injectable preparation as potential agents capable of delaying the aging of not only the skin but also the whole organism, which may be a component of the healthy aging concept.