Deoxynivalenol-induced circadian CLOCK oscillation disruption promotes RAW264.7 macrophage immunosenescence by unleashing cGAS–STING signaling

Treatment with 2 μM deoxynivalenol (DON) for 24 hours disrupted CLOCK expression and increased signs of immunosenescence in macrophages.

• DON exposure resulted in increased SA-β-gal activity, altered membrane morphology, and upregulation of cell cycle inhibitors p21 and p16.
• Elevated secretion of inflammatory markers IL-6, IL-8, and CCL-2 was observed following DON treatment.
• Blocking CLOCK for 4 to 12 hours after DON exposure worsened senescent features and increased cell death.
• DON activated the cGAS-STING pathway, leading to increased expression of cGAS, phosphorylated STING, and other downstream signaling components.
• Inhibition of STING reduced DON-induced senescence and apoptosis, highlighting its role in the process.
• CLOCK appears to negatively regulate the activation of the cGAS-STING pathway, contributing to DON-induced immunosenescence.

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