From mechanism to application: Harnessing oxidative stress signaling for innovative food design.

Abstract

As a central pathological process in aging and chronic diseases, oxidative stress (OS) stems from redox imbalance and propagates cellular damage through tightly linked signaling networks. Traditional functional food approaches, which focus on single-pathway interventions, fail to counter the complex crosstalk and compensatory adaptations seen in OS-related pathologies. In this article, we provide a systematic analysis of six key signaling pathways, namely Nrf2/ARE, FOXO, NF-κB, p53, SIRT1, and AMPK, and delineate their hierarchical structure and functional interactions in modulating antioxidant defense, metabolic reprogramming, and cell fate. We advocate for a multi-pathway synergistic strategy, rooted in rational systemic nutrition, to achieve coordinated control over redox balance, inflammatory responses, and metabolic homeostasis, thereby delivering efficacy beyond conventional single-target paradigms. To tackle persistent challenges such as nonlinear dose responses and interspecies metabolic variation, we propose a data-driven design framework that combines computational prediction, physiologically based pharmacokinetic modeling, and spatiotemporally precise nutrient delivery systems. Integrated with deep learning and human-relevant validation platforms, for instance organ-on-a-chip technology and multi-omics profiling, this framework accelerates the creation of personalized functional foods suited to individual physiological requirements. Our findings establish a theoretical basis for network-based nutritional design, driving the evolution of functional foods from empirical recipes to precision tools for systemic health restoration.