Protective Effects of an Ergothioneine‐Rich Serum Against Oxidative Stress‐Induced Senescence in Human Dermal Fibroblasts

ABSTRACT Ergothioneine (EGT) and vitamin C are potent antioxidants with the potential to mitigate oxidative stress and delay aging processes. This study investigates the effects of an antioxidant‐rich serum combination containing EGT and vitamin C on human dermal fibroblast cells. This study aimed to evaluate the potential antiaging effects of an antioxidant‐rich serum on an H 2 O 2 ‐induced senescence model in HDFa cells using biochemical, molecular, and analytical methods. After H 2 O 2 ‐induced oxidative stress, a significant reduction in the number of SA‐β‐galactosidase‐positive cells was observed in the serum‐treated group, with a 61.75% senescence rate, compared to 97.52% in the H 2 O 2 ‐treated cells. The serum demonstrated antioxidant properties, increasing total antioxidant capacity to 2.52 mmol Trolox equiv/g protein and reducing total oxidative status to 64.86 µmol H 2 O 2 equiv/g protein, indicating its effectiveness in combating oxidative stress. At the molecular level, the serum downregulated MMP‐1 and MMP‐3 expression and upregulated COL1A1 gene expression, suggesting its role in protecting extracellular matrix integrity and slowing aging. Additionally, apoptosis and cell cycle analysis indicated that the serum mitigates apoptosis and regulates cell cycle progression under oxidative stress. These findings highlight the potential of the EGT and vitamin C‐based antioxidant‐rich serum as an effective antiaging and oxidative stress‐reducing treatment for the skin.