REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicMetabolic Crossroads: Decoding the Immune-Tumor Interface for Therapeutic BreakthroughsView all articles
Aging-Associated Mechanisms and Metabolic Vulnerabilities in Esophageal Carcinoma: An Integrative Review
Provisionally accepted
- 1Key Laboratory of Cell Behavior,Medical School of Xuchang University,, Xuchang Henan 461000, China
- 2College of Chemical and Materials Engineering, Xuchang University, Xuchang Henan 461000, China
- 3Department of Stomatology, Xuchang Central Hospital, Xuchang Henan 461000, China
- 4Department of Mathematics and Physics, Luoyang Institute of Science and Technology, Luoyang, Henan 471023, China
- 5State Key Laboratory ofEsophageal CancerPrevention & Treatment, Luoyang 471003, China
- 6Henan Key Laboratory ofMicrobiome and Esophageal CancerPrevention and Treatment, Luoyang 471003, China
- 7Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology,, Luoyang 471003, China
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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.
Keywords: esophageal cancer, Aging, Metabolism, Tumor Microenvironment, senescence, immunosenescence
Received: 28 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Liu, Xie, Li, Li and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yijun Qi, qiqiyijun@163.com
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