Immunosenescence of microglia and macrophages: impact on the ageing central nervous system
Immunosenescence of microglia and macrophages: impact on the ageing central nervous system
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DOI：
10.1093/brain/awv395
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发表时间：
2016-03-01
期刊：
影响因子：
14.5
通讯作者：
Yong, V. Wee
中科院分区：
文献类型：
--
作者：
Rawji, Khalil S.;Mishra, Manoj K.;Yong, V. Wee
神经系统自我修复的能力随着年龄的增长而下降。Rawji等人。讨论衰老对神经系统疾病的影响，并提出其中一些影响可能反映了巨噬细胞和小胶质细胞的不同衰老。逆转巨噬细胞/小胶质细胞衰老的治疗策略可能会促进老化神经系统的再生。神经系统自我修复的能力随着年龄的增长而下降。Rawji等人。讨论衰老对神经系统疾病的影响，并提出其中一些影响可能反映了巨噬细胞和小胶质细胞的不同衰老。逆转巨噬细胞/小胶质细胞衰老的治疗策略可能会促进老化神经系统的再生。中枢神经系统的衰老会导致灰质和白质的丧失，导致认知能力下降。灰质和白质的额外损伤在许多随年龄增长的神经疾病中都有记录，包括阿尔茨海默病、创伤性脑和脊髓损伤、中风和多发性硬化症。伴随着神经元和神经胶质损伤的是由激活的巨噬细胞和小胶质细胞组成的炎症反应，天然免疫细胞在神经修复中既有益又有害。本文将提出如下建议：(I)巨噬细胞不同于中枢神经系统固有的小胶质细胞；(Ii)这两种不同类型细胞的不同衰老过程背后的几种机制；以及(Iii)选择性地针对这些不同机制的治疗策略可能会使巨噬细胞和小胶质细胞恢复活力，以修复老化的中枢神经系统。巨噬细胞的大多数反应随着衰老而减弱，但激活的小胶质细胞增加了其促炎细胞因子的表达，同时降低了趋化和吞噬活性。巨噬细胞和小胶质细胞的衰老对一些神经系统疾病有负面影响，其与年龄相关的表型变化的机制从外部微环境变化到基因组完整性的内在变化。我们讨论了AGE对神经系统疾病的负面影响，检查了衰老的巨噬细胞和小胶质细胞在这些条件下的反应，并提出了针对这两种不同类型细胞中导致衰老表型的不同机制的治疗策略的理论框架。老化的巨噬细胞/小胶质细胞的年轻化可以保持神经的完整性，并促进老化的中枢神经系统的再生。
The nervous system's capacity to repair itself declines with age. Rawji et al. discuss the effects of ageing on neurological diseases and propose that some of these effects may reflect differential senescence of macrophages and microglia. Therapeutic strategies to reverse macrophage/microglia senescence may promote regeneration in the ageing nervous system.The nervous system's capacity to repair itself declines with age. Rawji et al. discuss the effects of ageing on neurological diseases and propose that some of these effects may reflect differential senescence of macrophages and microglia. Therapeutic strategies to reverse macrophage/microglia senescence may promote regeneration in the ageing nervous system.Ageing of the central nervous system results in a loss of both grey and white matter, leading to cognitive decline. Additional injury to both the grey and white matter is documented in many neurological disorders with ageing, including Alzheimer's disease, traumatic brain and spinal cord injury, stroke, and multiple sclerosis. Accompanying neuronal and glial damage is an inflammatory response consisting of activated macrophages and microglia, innate immune cells demonstrated to be both beneficial and detrimental in neurological repair. This article will propose the following: (i) infiltrating macrophages age differently from central nervous system-intrinsic microglia; (ii) several mechanisms underlie the differential ageing process of these two distinct cell types; and (iii) therapeutic strategies that selectively target these diverse mechanisms may rejuvenate macrophages and microglia for repair in the ageing central nervous system. Most responses of macrophages are diminished with senescence, but activated microglia increase their expression of pro-inflammatory cytokines while diminishing chemotactic and phagocytic activities. The senescence of macrophages and microglia has a negative impact on several neurological diseases, and the mechanisms underlying their age-dependent phenotypic changes vary from extrinsic microenvironmental changes to intrinsic changes in genomic integrity. We discuss the negative effects of age on neurological diseases, examine the response of senescent macrophages and microglia in these conditions, and propose a theoretical framework of therapeutic strategies that target the different mechanisms contributing to the ageing phenotype in these two distinct cell types. Rejuvenation of ageing macrophage/microglia may preserve neurological integrity and promote regeneration in the ageing central nervous system.