8-Oxoguanine DNA glycosylase protects cells from senescence via the p53-p21 pathway

• OGG1 deficiency exacerbates bleomycin-induced cellular senescence in lung cells, characterized by increased SA-β-gal positivity and elevated p21 and p-H2AX levels. • OGG1 overexpression reverses senescence markers, promotes cell cycle progression, and maintains TERT and LaminB1 levels in BLM-treated cells. • OGG1 binds to p53, inhibiting its activation; silencing p53 reverses OGG1's protective effect, implicating the p53-p21 pathway as a key mediator. • In vivo, OGG1-deficient mice show augmented senescence, suggesting OGG1 as a potential therapeutic target for pulmonary fibrosis and aging-related lung diseases.