Population aging has increased the number of patients aged 65 years or older with cancer undergoing surgery; however, chronological age alone does not adequately capture perioperative vulnerability. Inflammaging, a chronic low-grade inflammatory state that accompanies aging, may provide a biological framework for understanding the heterogeneity of perioperative risk. Senescent-cell accumulation and the senescence-associated secretory phenotype contribute to persistent inflammatory signaling, while age-related immune remodeling produces an “immune paradox” involving heightened inflammatory signaling despite impaired immune effector function. Surgical stress may act as a second hit in this pre-existing state by amplifying damage-associated molecular pattern signaling, neuroendocrine activation, and perioperative immune dysfunction. These changes provide plausible links to impaired antitumor immune surveillance, infection, pulmonary complications, delirium, and delayed recovery but do not establish an inflammaging-mediated causal pathway to clinical outcomes. In this review, established perioperative care is discussed along with investigational approaches to immune-inflammatory modulation. Relevant approaches include prehabilitation, pathways for enhanced recovery after surgery, opioid-sparing multimodal analgesia, regional anesthesia, individualized anesthetic selection, and selected pharmacological adjuncts. Preoperative assessment of sarcopenia, serum albumin, and the neutrophil-to-lymphocyte ratio may complement the assessment of physiological vulnerability but does not specifically quantify inflammaging. Future studies should evaluate biomarker-guided risk stratification and determine whether anesthetic interventions have different effects according to biological aging and inflammaging status.
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Park et al. (2026) studied this question.
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