Bracken Olivia V, De Maeyer Roel P H, Akbar Arne N
Division of Medicine, University College London, London, UK.
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Nat Rev Drug Discov. 2025 Apr;24(4):300-315. doi: 10.1038/s41573-024-01126-9. Epub 2025 Jan 28.
Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as 'inflammageing'. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone. We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissues.
免疫力会随着年龄的增长而下降。这会导致患与年龄相关疾病的风险更高，对新感染的反应能力减弱以及对疫苗的反应降低。这种免疫功能障碍的原因是细胞衰老，其发生在淋巴组织和非淋巴组织中，以及被称为“炎症衰老”的慢性低度炎症。在这篇综述文章中，我们强调炎症和衰老过程如何相互驱动，导致免疫功能丧失。为了打破这个循环，需要针对改变的组织环境与免疫系统之间的相互作用的疗法，而不是单独针对每个组成部分。我们在组织微环境的背景下讨论了旨在消除衰老细胞的疗法（衰老细胞溶解剂）和抑制炎症的疗法（衰老细胞形态调节剂）的相对优缺点。此外，我们还讨论了旨在直接增强免疫细胞功能和改善组织中免疫监视的治疗策略。
