Goldberg Emily L, Shaw Albert C, Montgomery Ruth R
Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Interdiscip Top Gerontol Geriatr. 2020;43:1-17. doi: 10.1159/000504480. Epub 2020 Apr 9.
The collective loss of immune protection during aging leads to poor vaccine responses and an increased severity of infection for the elderly. Here, we review our current understanding of effects of aging on the cellular and molecular dysregulation of innate immune cells as well as the relevant tissue milieu which influences their functions. The innate immune system is composed of multiple cell types which provide distinct and essential roles in tissue surveillance and antigen presentation as well as early responses to infection or injury. Functional defects that arise during aging lead to a reduced dynamic range of responsiveness, altered cytokine dynamics, and impaired tissue repair. Heightened inflammation influences both the dysregulation of innate immune responses as well as surrounding tissue microenvironments which have a critical role in development of a functional immune response. In particular, age-related physical and inflammatory changes in the skin, lung, lymph nodes, and adipose tissue reflect disrupted architecture and spatial organization contributing to diminished immune responsiveness. Underlying mechanisms include altered transcriptional programming and dysregulation of critical innate immune signaling cascades. Further, we identify signaling functions of bioactive lipid mediators which address chronic inflammation and may contribute to the resolution of inflammation to improve innate immunity during aging.
衰老过程中免疫保护的集体丧失导致老年人疫苗反应不佳以及感染严重程度增加。在此，我们综述了目前对衰老对固有免疫细胞的细胞和分子失调以及影响其功能的相关组织微环境的影响的理解。固有免疫系统由多种细胞类型组成，这些细胞在组织监测、抗原呈递以及对感染或损伤的早期反应中发挥着独特而重要的作用。衰老过程中出现的功能缺陷导致反应性动态范围缩小、细胞因子动态改变以及组织修复受损。炎症加剧既影响固有免疫反应的失调，也影响周围组织微环境，而周围组织微环境在功能性免疫反应的发展中起着关键作用。特别是，皮肤、肺、淋巴结和脂肪组织中与年龄相关的物理和炎症变化反映了结构和空间组织的破坏，导致免疫反应性降低。潜在机制包括转录程序改变和关键固有免疫信号级联的失调。此外，我们确定了生物活性脂质介质的信号功能，这些介质可解决慢性炎症，并可能有助于炎症的消退，以改善衰老过程中的固有免疫力。
