The identification of reliable biomarkers of ageing represents a major challenge in biomedical research, particularly in the context of increasing life expectancy and the growing burden of chronic diseases. Among potential candidates, the ABO blood group system has attracted interest as a stable genetic trait potentially associated with inter-individual variability in ageing-related outcomes. This narrative review critically examines current evidence linking ABO blood groups to age-related diseases and biological mechanisms of ageing. A structured search of major biomedical databases was performed, focusing primarily on studies published in the last five years and complemented by seminal earlier reports. Current findings indicate associations between ABO phenotypes and several chronic conditions, including cardiovascular disease, thrombotic disorders, diabetes, cancer, allergies, and cognitive disorders, which substantially contribute to morbidity and mortality in older adults. However, data are contradictory and dependent on ethnicity, genetic background and environmental factors. Non-O blood groups consistently exhibit a higher risk of thrombotic and cardiovascular events, likely mediated by differences in coagulation factors, endothelial function, and hemostatic balance. ABO-related phenotypic variation may also influence processes implicated in ageing, including vascular dysfunction, chronic low-grade inflammation, immune remodeling, glycosylation pathways, cellular senescence, and host-microbiome interactions. However, evidence supporting a direct relationship between ABO blood groups and longevity remains inconsistent and appears to be population dependent. Overall, current data suggest that ABO blood groups are unlikely to represent independent biomarkers of ageing, but rather modest, context-dependent modifiers of biological pathways contributing to susceptibility to age-related diseases. Further longitudinal and mechanistic studies are needed to clarify their role in healthy and pathological ageing trajectories. SUMMARY: ABO blood group system has been associated with susceptibility to several age-related diseases (ARDs). Non-O blood groups show a higher risk of thrombotic and cardiovascular events. Although some studies also suggest a relationship between ABO phenotype and longevity, findings remain inconsistent and appear to vary across populations. Potential mechanisms linking ABO blood groups to ageing include effects on inflammation, vascular function, immune responses, and host-microbiome interactions. Overall, current evidence indicates that ABO blood group is unlikely to represent an independent biomarker of ageing, but rather a modest and context-dependent factor that can influence aging-related mechanisms and contribute to the ARD development.
