Fetarayani Deasy, Kahdina Mega, Waitupu Alief, Pratiwi Laras, Ningtyas Mukti Citra, Adytia Galih Januar, Sutanto Henry
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia.
Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia.
Med Sci (Basel). 2025 Jul 28;13(3):100. doi: 10.3390/medsci13030100.
Aging is associated with complex immune dysfunction that contributes to the onset and progression of the "geriatric giants", including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation-or "inflammaging"-amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions-ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise-that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction.
衰老与复杂的免疫功能障碍相关，这种免疫功能障碍会促使包括衰弱、肌肉减少症、认知衰退、跌倒和尿失禁在内的“老年巨症”的发生和发展。这些情况的核心是免疫衰老，其特征为胸腺退化、初始T细胞丧失、T细胞耗竭、B细胞类别转换重组受损以及自身反应性增加。与此同时，由于巨噬细胞、中性粒细胞和自然杀伤细胞功能障碍，固有免疫会恶化，而慢性低度炎症（即“炎症衰老”）会加剧全身衰退。诸如核因子κB、哺乳动物雷帕霉素靶蛋白和NLRP3炎性小体等关键分子途径介导免疫衰老，与氧化应激、线粒体功能障碍和表观遗传修饰相互作用。这些过程不仅会损害感染控制和疫苗反应性，还会促进组织退化和多种疾病的发生。本综述探讨了从衰老细胞溶解剂、免疫营养到针对微生物群的疗法和运动等新兴干预措施，这些措施可能恢复免疫稳态并延长健康期。尽管取得了进展，但将免疫学见解转化为针对老年人的临床策略仍面临挑战。微生物群试验的标准化和衰老细胞溶解疗法的安全性优化是关键的下一步。将老年科学融入临床护理有助于通过针对免疫功能障碍的根本驱动因素来减轻与衰老相关疾病的负担。
