Aging-associated mechanisms and metabolic vulnerabilities in esophageal carcinoma: an integrative review

Esophageal carcinoma (EC), comprising esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), remains a deadly malignancy predominantly affecting individuals over 60 years of age. Although advances in diagnosis and treatment have improved outcomes for some cancers, EC still carries a poor prognosis, particularly in the elderly. Aging contributes significantly to EC pathogenesis via accumulated genetic mutations, metabolic deregulation, immunosenescence, and a pro-tumorigenic microenvironment. In this review, we synthesize current understanding of the molecular alterations that drive EC, with particular emphasis on age-related factors. We examine key genomic mutations (e.g., TP53, chromosomal instability), metabolic reprogramming (including glycolysis, glutaminolysis, and lipid metabolism), and their interplay with the tumor microenvironment (TME). We also highlight the influence of aging processes such as clonal hematopoiesis, senescence-associated secretory phenotype (SASP), and immune exhaustion in modulating tumor behavior and therapeutic resistance. We propose that aging-associated metabolic and immunologic alterations represent promising targets for therapeutic intervention. Greater integration of aging biology into EC research and clinical strategy is needed to advance personalized care for elderly patients. This review provides a conceptual foundation for future translational and clinical studies at the intersection of oncology and aging.