Fig. 1: Oxidative stress-immunometabolic crosstalk as a shared axis in aging and tumorigenesis, and its therapeutic targeting by traditional Chinese medicine (TCM).

This schematic elucidates the mechanistic convergence of oxidative stress and immunometabolic dysregulation in aging and cancer pathogenesis, alongside TCM interventions bridging both diseases. The upper panel illustrates anti-aging TCM formulations (e.g., Astragali Radix, Lycii Fructus), while the lower panel highlights anti-tumor TCM agents (e.g., Astragalus polysaccharides, Baicalin), with overlapping components (e.g., Astragali Radix-derived compounds) emphasizing their dual therapeutic potential. Physiological redox balance (left): Controlled oxidative eustress (ROS/antioxidant equilibrium) sustains redox-sensitive signaling and immunometabolic homeostasis in innate/adaptive immune cells (NK cells, T cells, macrophages). This enables efficient immunosurveillance against damaged or transformed cells through balanced glycolysis and mitochondrial respiration. ROS sources (middle): Mitochondrial dysfunction, NADPH oxidases, and xenobiotics generate ROS subtypes (e.g., O²⁻, H₂O₂) that disrupt redox signaling. Notably, aging-associated mitochondrial decay and cancer-driven Warburg effect synergistically amplify ROS production. Pathological crosstalk (right): Sustained oxidative stress triggers a vicious cycle: Immunometabolic paralysis: Excessive ROS impair immune cell metabolic adaptation (e.g., suppressed glucose utilization, defective lipid oxidation), compromising cytotoxic activity and antigen presentation. Redox signaling collapse: Dysregulated redox networks deplete antioxidant defenses (e.g., SOD, CAT) while amplifying pro-inflammatory cytokine release, fostering a chronic inflammatory microenvironment. Disease convergence: This dual failure enables the survival of redox-damaged cells, driving senescent cell accumulation and malignant clone expansion through oxidative DNA damage and impaired repair mechanisms, thereby accelerating both tissue aging and tumor progression. Anti-aging interventions (top): Classical formulations (e.g., Astragali Radix, Lycii Fructus) ameliorate age-related pathologies by modulating oxidative stress-immunometabolic crosstalk, particularly through mitochondrial ROS regulation and metabolic reprogramming of senescent immune cells. Anti-aging interventions (bottom): Multi-herb formulations (e.g., Bu Shen Huo Xue Decoction) and bioactive compounds (e.g., Baicalin) counteract tumor progression via dual regulation of redox homeostasis and immunometabolic rewiring in tumor-associated immune cells. TCM therapeutic advantages: TCM leverages shared components (e.g., Astragali Radix, Huangqi Baihe Granules) to concurrently mitigate oxidative damage in aging tissues and tumor microenvironments through redox homeostasis regulation, rejuvenate immunometabolic function. This synergistic strategy positions TCM as a unique paradigm for managing aging-cancer comorbidities, particularly in elderly patients with age-related malignancies.