Ortega-Sollero, EnriqueRuíz-Fernández, IgnacioMartín, Pilar2026-03-202026-03-202025-05-30Journal of Cardiovascular Aging, 2025. 5(2).2768-5993https://hdl.handle.net/20.500.12105/27345Aging alters the immune system, leading to immunosenescence characterized by impaired T cell functions. The balance between regulatory T cells and type 17 helper T (Th17) cells is crucial for maintaining peripheral immune homeostasis. Aging disrupts this balance, contributing to a systemic chronic proinflammatory environment that increases the prevalence of age-related diseases. The Treg/Th17 imbalance compromises self-tolerance, promoting autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Furthermore, chronic inflammation driven by aberrant T cell responses is a significant risk factor for the progression of cardiovascular diseases (CVD), including hypertension, atherosclerosis, myocardial infarction, and myocarditis. Autoimmune disorders further exacerbate the risk of CVD, which remains the leading cause of mortality among patients with autoimmune diseases. This review provides an in-depth analysis of the mechanisms driving Treg/Th17 imbalance during aging, highlighting its impact on immune homeostasis, autoimmunity, and cardiovascular health. It explores how inflammaging and T cell dysfunction contribute to diseases such as rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, and myocardial infarction, emphasizing shared pathways and therapeutic strategies to restore immune balance and mitigate chronic inflammation. Understanding these immune pathways highlights the therapeutic potential of restoring Treg/Th17 balance to restore immune tolerance and reduce chronic inflammation, thereby mitigating the onset and progression of these age-related conditions.Martín P is supported by grants from the Madrid Regional Government (S2022/BMD-7209- INTEGRAMUNE-CM), MCIN-ISCIII-Fondo de Investigación Sanitaria (PI22/01759), co-funded by the European Regional Development Fund, PMPTA22/00090-BIOCARDIOTOX, co-funded by NextGEN, and the Fundació La Marató TV3 (grant 202325 30 31). Ruíz-Fernández I is supported by a Formación de Profesorado Universitario grant (FPU20/05176). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International5210.20517/jca.2024.40Journal of Cardiovascular Agingopen access