Bulut Ozlem, Koeken Valerie A C M, Moorlag Simone J C F M, de Bree Charlotte J, Mourits Vera P, Kilic Gizem, Debisarun Priya A, Baltissen Marijke P A, Martens Joost H A, Domínguez-Andrés Jorge, Joosten Leo A B, Netea Mihai G
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, the Netherlands.
iScience. 2025 Jul 18;28(8):113159. doi: 10.1016/j.isci.2025.113159. eCollection 2025 Aug 15.
This study explores the effects of Bacillus Calmette-Guérin (BCG) vaccination on telomere maintenance, an aging-related process, in immune cells. While BCG reduces systemic inflammation and enhances innate immune responsiveness by inducing trained immunity, its effects on other immune aging hallmarks, such as telomere shortening, are not fully understood. We assessed telomere length in two independent human cohorts before and three months after BCG vaccination. Telomere shortening was consistently observed after BCG, but not after placebo vaccination. Trained immunity non-responders were likelier to lose telomere length, but only among males. Higher pre-vaccination testosterone levels were associated with greater telomere loss in males. , BCG training activated telomerase, particularly in females, and this was partially prevented by exogenous testosterone. These findings suggest BCG vaccination influences telomere dynamics in a sex-specific manner, contributing to understanding BCG's broader effects on aging-related processes.
本研究探讨卡介苗（BCG）接种对免疫细胞中端粒维持（一个与衰老相关的过程）的影响。虽然卡介苗通过诱导训练免疫来减轻全身炎症并增强先天免疫反应性，但其对其他免疫衰老特征（如端粒缩短）的影响尚未完全明确。我们在两个独立的人类队列中评估了卡介苗接种前及接种后三个月的端粒长度。接种卡介苗后持续观察到端粒缩短，但接种安慰剂后未出现。训练免疫无反应者更有可能出现端粒长度丢失，但仅在男性中如此。接种前较高的睾酮水平与男性更大的端粒丢失相关。此外，卡介苗训练激活了端粒酶，尤其是在女性中，而外源性睾酮可部分阻止这种激活。这些发现表明卡介苗接种以性别特异性方式影响端粒动态，有助于理解卡介苗对与衰老相关过程的更广泛影响。
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