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

Salvatore Chirumbolo1, Luigi Valdenassi2, Dario Bertossi3

  • 1Department of Engineering for Innovation Medicine, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy. salvatore.chirumbolo@univr.it.

Biogerontology
|December 23, 2025
PubMed
Abstract

Insights

Oxygen-ozone therapy (OOT) may promote healthy aging by inducing adaptive chaos in the redox-inflammatory pathway. A computational model suggests a specific ozone dose range may enhance cellular resilience, particularly in deficient systems.

Area of Science:

  • Biogerontology
  • Systems Biology
  • Computational Modeling

Background:

  • Aging is associated with declining redox adaptability and increased inflammation.
  • The HMGB1-Nrf2 pathway plays a critical role in cellular redox homeostasis and inflammatory responses.
  • Oxygen-ozone therapy (OOT) is being investigated for its potential health benefits.

Purpose of the Study:

  • To computationally evaluate if OOT can modulate aging processes.
  • To investigate the induction of adaptive chaos in the HMGB1-Nrf2 redox-inflammatory pathway by OOT.
  • To explore the dose-dependent effects of ozone on cellular systems.

Main Methods:

  • A computational systems biology model was developed.
  • Simulated feedback loops involving ROS, Nrf2, HMGB1, and NF-κB.
  • Varied ozone doses and cellular contexts (protective vs. autophagy-deficient) were modeled.

Main Results:

  • Intermediate ozone doses induced controlled chaos in the simulated system.
  • A potential 'chaotic window' of 30-40 μg/mL ozone was identified.
  • This window may enhance redox resilience in autophagy-deficient cells.

Conclusions:

  • OOT might contribute to healthy aging by modulating redox adaptability.
  • Theoretical effectiveness is dose-dependent, beneficial for aged/dysfunctional systems.
  • The model provides insights but requires experimental validation for real-world predictions.
Keywords:
AgingBioinformaticsHMGB1Ozone therapy

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