Aging-associated changes in the immune system often lead to immune dysfunction; however, the mechanisms that underlie this phenomenon have yet to be fully elucidated. This study found that the microRNA-192 (miR-192) is an aging-associated immune regulatory microRNA whose concentration was significantly increased in aged extracellular vesicles (EVs) due to the hyperinflammatory state of aged mice. Interestingly, EV miR-192 exhibited anti-inflammatory effects on macrophages. In our aged mouse model, aging was associated with prolonged inflammation in the lung upon stimulation with inactivated influenza whole virus particles (WVP), whereas EV miR-192 alleviated the prolonged inflammation associated with aging. The hyperinflammatory state of aged mice resulted in reduced production of specific antibodies and efficacy of vaccination with WVP; however, EV miR-192 attenuated this hyperinflammatory state and improved vaccination efficacy in aged mice. Our data indicate that aged EVs constitute a negative feedback loop that alleviates aging-associated immune dysfunction.

与衰老相关的免疫系统变化常常导致免疫功能障碍；然而，这一现象背后的机制尚未完全阐明。这项研究发现，microRNA-192（miR-192）是一种与衰老相关的免疫调节microRNA，由于衰老小鼠的高炎症状态，其浓度在衰老的细胞外囊泡（EV）中显着增加。有趣的是，EV miR-192 对巨噬细胞表现出抗炎作用。在我们的老年小鼠模型中，衰老与灭活流感全病毒颗粒（WVP）刺激后肺部的长期炎症有关，而 EV miR-192 减轻了与衰老相关的长期炎症。老年小鼠的高炎症状态导致特异性抗体的产生和 WVP 疫苗接种效果的降低；然而，EV miR-192 减轻了老年小鼠的这种过度炎症状态并提高了疫苗接种效果。我们的数据表明，老化的电动汽车构成了一个负反馈回路，可以缓解与衰老相关的免疫功能障碍。