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星形胶质细胞的虚弱和功能丧失,而不是反应性,导致大脑老化。

Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain.

机构信息

Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.

Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.

出版信息

Pflugers Arch. 2021 May;473(5):753-774. doi: 10.1007/s00424-020-02465-3. Epub 2020 Sep 26.

Abstract

Astroglia represent a class of heterogeneous, in form and function, cells known as astrocytes, which provide for homoeostasis and defence of the central nervous system (CNS). Ageing is associated with morphological and functional remodelling of astrocytes with a prevalence of morphological atrophy and loss of function. In particular, ageing is associated with (i) decrease in astroglial synaptic coverage, (ii) deficits in glutamate and potassium clearance, (iii) reduced astroglial synthesis of synaptogenic factors such as cholesterol, (iv) decrease in aquaporin 4 channels in astroglial endfeet with subsequent decline in the glymphatic clearance, (v) decrease in astroglial metabolic support through the lactate shuttle, (vi) dwindling adult neurogenesis resulting from diminished proliferative capacity of radial stem astrocytes, (vii) decline in the astroglial-vascular coupling and deficient blood-brain barrier and (viii) decrease in astroglial ability to mount reactive astrogliosis. Decrease in reactive capabilities of astroglia are associated with rise of age-dependent neurodegenerative diseases. Astroglial morphology and function can be influenced and improved by lifestyle interventions such as intellectual engagement, social interactions, physical exercise, caloric restriction and healthy diet. These modifications of lifestyle are paramount for cognitive longevity.

摘要

星形胶质细胞是一类形态和功能多样的细胞,被称为星形胶质细胞,它们为中枢神经系统(CNS)的内环境稳定和防御提供支持。随着年龄的增长,星形胶质细胞会发生形态和功能的重塑,表现为形态萎缩和功能丧失。特别是,衰老与(i)星形胶质细胞突触覆盖面积减少,(ii)谷氨酸和钾清除功能缺陷,(iii)突触发生因子如胆固醇的合成减少,(iv)星形胶质细胞终足中的水通道蛋白 4 通道减少,随后出现神经淋巴清除功能下降,(v)通过乳酸穿梭的星形胶质细胞代谢支持减少,(vi)由于放射状干细胞星形胶质细胞增殖能力下降导致成年神经发生减少,(vii)星形胶质细胞-血管偶联下降和血脑屏障功能缺陷,以及(viii)星形胶质细胞发生反应性星形胶质细胞增生的能力下降。星形胶质细胞反应能力的下降与年龄相关性神经退行性疾病的发生有关。通过生活方式干预,如智力活动、社交互动、体育锻炼、热量限制和健康饮食,可以影响和改善星形胶质细胞的形态和功能。这些生活方式的改变对于认知长寿至关重要。

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