A conceptual model of oxygen-ozone therapy as a modulator of aging via the HMGB1 pathway

OBJECTIVES: To evaluate whether oxygen-ozone therapy (OOT) can modulate aging by inducing adaptive chaos in the HMGB1-Nrf2 redox-inflammatory pathway. METHODS: A computational systems biology model simulated feedback loops among ROS, Nrf2, HMGB1, and NF-κB under varying ozone doses and cellular contexts (protective vs. autophagy-deficient). RESULTS: Intermediate ozone doses in the model triggered controlled chaos. The model suggests a potential 'chaotic window' (30-40 μg/mL ozone) that may promote redox resilience in autophagy-deficient cells. CONCLUSION: OOT may potentially contribute to healthy aging by modulating redox adaptability. Its theoretical effectiveness is dose-dependent, with maximal benefit in aged or dysfunctional systems requiring reactivation of flexible stress responses. However, while the model offers insights into possible dynamic behaviours of the redox-inflammatory axis under ozone exposure, it is not yet calibrated to biological data and cannot predict real-world outcomes without further experimental support.