Low-dose ionizing radiation promotes lifespan extension and stress resistance of C. elegans via DAF-16/SKN-1 mediated adaptive response.

Exposure to ionizing radiation (IR) has raised significant concern regarding potential health risks, particularly the frailty-like syndromes. Paradoxically, emerging evidence suggests that low-dose IR exposure may exert opposite effects. In this study, we show that exposure to 0.5 and 2.0 Gy X-rays extends lifespan in C. elegans. We demonstrate that elevated levels of persistent reactive oxygen species (ROS) and mitochondrial ROS induced by low-dose IR act as key drivers in activating the transcription factors (TFs) DAF-16 and SKN-1 in C. elegans. Additionally, we elucidate that under low-dose IR exposure, DAF-16 regulates the expression of skn-1, while SKN-1 binds to the promoters of antioxidant genes through a conserved motif, thereby initiating adaptive responses that maintain redox homeostasis, enhance stress resistance, and ultimately promote lifespan extension. This work identifies a critical regulatory network that drives lifespan extension and stress resistance in C. elegans, and provides candidate targets and mechanistic insights for preventive interventions aimed at mitigating IR-induced aging and lifespan shortening.