Frontiers in Immunology · Oct 9, 2026

Redox signaling fidelity in immunosenescence and inflammaging: from oxidative stress to precision immune geroscience

By Lu W, Yan J

Immunosenescence and inflammaging are accompanied by chronic inflammatory tone, impaired host-defense responses, defective resolution, and altered immunometabolic adaptation. Although these processes are often linked to oxidative stress, reactive oxygen species (ROS) also function as regulated immune signals. Here, we propose that aging immunity may involve not only increased oxidant burden but also a progressive loss of redox signaling fidelity, defined as the capacity of immune cells and tissues to generate, encode, transmit, decode, and resolve redox-dependent information with source specificity, spatially organized routing, temporal precision, biochemical reversibility, and proportionate downstream interpretation. We organize this framework into five information-flow layers: source-controlled reactive-species generation, reversible cysteine-centered and secondary-mediator encoding, spatially organized transmission, immune and inflammatory decoding, and resolution/reset by antioxidant, autophagy, mitophagy, lysosomal, and proteostatic systems. We then map age-associated fidelity loss onto T cells, B cells and hematopoietic progenitors, macrophages and microglia, neutrophils, dendritic cells, natural killer cells, regulatory T cells, and senescent-cell communication. The framework helps explain why related redox signals can support host defense, antigen-specific activation, and adaptive stress responses in one context, yet promote maladaptive NF-kappaB, NLRP3, cGAS-STING, interferon-linked inflammation, and senescence-associated secretory propagation when source coupling, timing, spatial routing, reversibility, decoder proportionality, or resolution fails. We also discuss why broad antioxidant suppression may underperform when it lowers oxidant abundance while flattening adaptive redox dynamics. Finally, we outline quantitative metrics, decisive experiments, controversies, and biomarker-guided therapeutic principles for precision immune geroscience.

doi.org/10.3389/fimmu.2026.1908166Open accessPubMed 42921489Mechanisms