Inflammaging and cytokine-driven cardiovascular senescence in age-related myocardial infarction: mechanisms, biomarkers, and precision immunotherapy strategies.

Ageing is an independent, non-modifiable risk factor for myocardial infarction (MI). It is also characterized by chronic, low-grade inflammation (inflammaging) and progressive cardiovascular senescence. These ageing-associated processes alter cytokine networks and innate and adaptive immune-cell function, promote endothelial dysfunction, and compromise post-infarction repair, thereby increasing myocardial susceptibility to ischaemia and adverse cardiac remodelling in the elderly. Lifestyle modifications, including regular physical activity, reduce inflammaging by facilitating the release of anti-inflammatory cytokines and counteract cellular senescence. This review compiles current mechanistic and translational evidence connecting inflammaging to age-related myocardial infarction, focusing on cytokine-mediated immune interactions. Additionally, this review also examines age-related cytokine dysregulation in myocardial infarction, pro-inflammatory and anti-inflammatory cytokine networks, inflammasome-mediated pyroptosis, senescence-associated secretory phenotypes, and emerging cytokine and extracellular vesicle-based biomarkers. It further discusses translational advances in cytokine-targeted, senescence-directed, and precision immunology-guided therapeutic strategies for the ageing population. In conclusion, inflammaging is closely linked to age-related myocardial infarction, with the IL-6/IL-1 signalling axis supported by the most direct interventional evidence to date including outcome evidence from canakinumab (CANTOS) and phase 2 STEMI myocardial-salvage evidence from tocilizumab (ASSAIL-MI). Cytokine-based immunotherapies targeting this axis represent a promising therapeutic approach for age-related myocardial infarction, although their efficacy and safety in older populations remain to be established in dedicated clinical trials.