Ellagic Acid Mediates the Delay of Dermal Fibroblast Senescence via CSNK2A1

This research seeks to explore the impact of Ellagic Acid (EA) on the aging process of human dermal fibroblasts Hs68 cells and to uncover the mechanisms involved. Senescence was induced in Hs68 cells with H2O2, followed by treatment with EA and CSNK2A1 inhibitor (Silmitasertib). Bioinformatics identified EA's downstream targets. Cell viability was assessed by MTT assays, and senescence markers (γH2AX, p16, p19, p53), CSNK2A1, Nrf2, and NF-κB p65 were analyzed by Western blot. Inflammatory cytokines (IL-6, TNF-α, IL-1β) and oxidative stress markers (SOD, MDA, GSH/GSSG) were measured. ROS levels were assessed by fluorescence staining, senescence by SA-β-gal staining, cell cycle by flow cytometry and apoptosis by TUNEL assay. Senescent cells showed increased γH2AX, p16, p19, and p53 expression, with reduced viability. EA inhibited senescence in a dose-dependent manner, with cytotoxicity at 60 μM. EA upregulated CSNK2A1, decreased β-galactosidase activity, restored cell viability and cycle progression, and reduced apoptosis. EA alleviated oxidative stress by enhancing Nrf2 expression, reducing ROS and MDA, and increasing SOD and GSH/GSSG. Silmitasertib negated these effects. EA also reduced IL-6, TNF-α, and IL-1β, inhibiting NF-κB p65, with anti-inflammatory effects mediated by CSNK2A1. EA delays dermal fibroblast senescence by modulating CSNK2A1, mitigating oxidative stress and inflammation, and may serve as a potential therapeutic for aging and age-related diseases.