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老年大脑中的神经母细胞衰老增强了自然杀伤细胞的细胞毒性,导致神经发生和认知受损。

Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition.

机构信息

China National Clinical Research Center for Neurological Diseases, Jing-Jin Center for Neuroinflammation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Nat Neurosci. 2021 Jan;24(1):61-73. doi: 10.1038/s41593-020-00745-w. Epub 2020 Nov 30.


DOI:10.1038/s41593-020-00745-w
PMID:33257875
Abstract

Normal aging is accompanied by escalating systemic inflammation. Yet the potential impact of immune homeostasis on neurogenesis and cognitive decline during brain aging have not been previously addressed. Here we report that natural killer (NK) cells of the innate immune system reside in the dentate gyrus neurogenic niche of aged brains in humans and mice. In situ expansion of these cells contributes to their abundance, which dramatically exceeds that of other immune subsets. Neuroblasts within the aged dentate gyrus display a senescence-associated secretory phenotype and reinforce NK cell activities and surveillance functions, which result in NK cell elimination of aged neuroblasts. Genetic or antibody-mediated depletion of NK cells leads to sustained improvements in neurogenesis and cognitive function during normal aging. These results demonstrate that NK cell accumulation in the aging brain impairs neurogenesis, which may serve as a therapeutic target to improve cognition in the aged population.

摘要

正常衰老伴随着不断加剧的系统性炎症。然而,免疫稳态对大脑衰老过程中神经发生和认知能力下降的潜在影响尚未得到解决。在这里,我们报告说,先天免疫系统的自然杀伤 (NK) 细胞存在于人类和小鼠衰老大脑的齿状回神经发生龛位中。这些细胞的原位扩增有助于增加其数量,其数量远远超过其他免疫亚群。衰老齿状回内的神经前体细胞表现出与衰老相关的分泌表型,并增强 NK 细胞的活性和监视功能,导致 NK 细胞清除衰老的神经前体细胞。NK 细胞的基因或抗体耗竭会导致正常衰老过程中神经发生和认知功能的持续改善。这些结果表明,衰老大脑中 NK 细胞的积累会损害神经发生,这可能成为改善老年人群认知能力的治疗靶点。

相似文献

[1]
Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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引用本文的文献

[1]
Modulation of adult hippocampal neurogenesis by interleukin 1 signaling.

Neurobiol Sleep Circadian Rhythms. 2025-4-25

[2]
Cellular senescence, neuroinflammation, and microRNAs: Possible interactions driving aging and neurodegeneration in the hippocampal neurogenic niche.

Aging Brain. 2025-6-12

[3]
Hallmarks of stem cell aging.

Cell Stem Cell. 2025-7-3

[4]
Cross-Analysis of Single-Cell Transcriptomic Datasets Reveals Conserved Neurogenic Gene Signatures and New Insights Into Neural Stem Cell Aging.

Aging Cell. 2025-8

[5]
Identification of Hub Genes and Pathways Associated with Ageing in Diabetic Encephalopathy Based on Transcriptome Analysis.

Biochem Genet. 2025-5-21

[6]
Brain injury, endocrine disruption, and immune dysregulation in HIV-positive men who have sex with men with late HIV diagnosis.

Front Immunol. 2025-3-19

[7]
Environmental Enrichment Exposure Alleviates Geriatric Depressive-Like Symptoms through Regulating Neurogenesis and Neuroinflammation.

Environ Health (Wash). 2024-11-20

[8]
NK cells: shielding senescence homeostasis in the decidua during early pregnancy.

Semin Immunopathol. 2025-3-11

[9]
Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation.

Cell Rep. 2025-2-18

[10]
The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis.

Sci Immunol. 2025-2-28

本文引用的文献

[1]
Cellular Senescence: Defining a Path Forward.

Cell. 2019-10-31

[2]
Single-cell analysis reveals T cell infiltration in old neurogenic niches.

Nature. 2019-7-3

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Nat Rev Neurol. 2019-6

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The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy.

Trends Immunol. 2019-1-10

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NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination.

Science. 2018-12-21

[6]
Cutting Edge: Local Proliferation of Uterine Tissue-Resident NK Cells during Decidualization in Mice.

J Immunol. 2018-10-1

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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.

Nat Rev Cardiol. 2018-9

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Nat Rev Endocrinol. 2018-10

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Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis.

Blood Adv. 2018-6-12

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Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

Nat Rev Neurol. 2018-3-23

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