Nga, Ha ThiNguyen, Thi LinhYi, Hyon-Seung2026-03-202026-03-202024-09Diabetes Metab J. 2024 Sep;48(5):864-881.https://hdl.handle.net/20.500.12105/27344Immunosenescence denotes a state of dysregulated immune cell function characterized by a confluence of factors, including arrested cell cycle, telomere shortening, markers of cellular stress, mitochondrial dysfunction, loss of proteostasis, epigenetic reprogramming, and secretion of proinflammatory mediators. This state primarily manifests during the aging process but can also be induced in various pathological conditions, encompassing chronic viral infections, autoimmune diseases, and metabolic disorders. Age-associated immune system alterations extend to innate and adaptive immune cells, with T-cells exhibiting heightened susceptibility to immunosenescence. In particular, senescent T-cells have been identified in the context of metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Recent investigations suggest a direct link between T-cell senescence, inflammation, and insulin resistance. The perturbation of biological homeostasis by senescent T-cells appears intricately linked to the initiation and progression of metabolic diseases, particularly through inflammation-mediated insulin resistance. Consequently, senescent T-cells are emerging as a noteworthy therapeutic target. This review aims to elucidate the intricate relationship between metabolic diseases and T-cell senescence, providing insights into the potential roles of senescent T-cells in the pathogenesis of metabolic disorders. Through a comprehensive examination of current research findings, this review seeks to contribute to a deeper understanding of the complex interplay between immunosenescence and metabolic health.This study was supported by the Korean Endocrine Society of KES Research Award 2023, and BK21 FOUR Program by Chungnam National University Research Grant, 2024. Hyon-Seung Yi was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning, Korea (NRF-2021R1A2C4001829) and supported by the Chungnam National University Hospital Research Fund (2023) and a grant from the Korea Health Technology R&D Project, through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant numbers: HR22C1734 and HI23C153400).engVoRAgingDiabetes mellitusMetabolic diseasesT-cell senescence39192822485Diabetes & Metabolism Journalopen access