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老年大脑中的神经元衰老

Neuronal Senescence in the Aged Brain.

作者信息

Chou Shu-Min, Yen Yu-Hsin, Yuan Fang, Zhang Su-Chun, Chong Cheong-Meng

机构信息

Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, 169857 Singapore, Singapore.

Department of Neuroscience, Department of Neurology, Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.

出版信息

Aging Dis. 2023 Oct 1;14(5):1618-1632. doi: 10.14336/AD.2023.0214.

Abstract

Cellular senescence is a highly complicated cellular state that occurs throughout the lifespan of an organism. It has been well-defined in mitotic cells by various senescent features. Neurons are long-lived post-mitotic cells with special structures and functions. With age, neurons display morphological and functional changes, accompanying alterations in proteostasis, redox balance, and Ca dynamics; however, it is ambiguous whether these neuronal changes belong to the features of neuronal senescence. In this review, we strive to identify and classify changes that are relatively specific to neurons in the aging brain and define them as features of neuronal senescence through comparisons with common senescent features. We also associate them with the functional decline of multiple cellular homeostasis systems, proposing the possibility that these systems are the main drivers of neuronal senescence. We hope this summary will serve as a steppingstone for further inputs on a comprehensive but relatively specific list of phenotypes for neuronal senescence and in particular their underlying molecular events during aging. This will in turn shine light on the association between neuronal senescence and neurodegeneration and lead to the development of strategies to perturb the processes.

摘要

细胞衰老一种高度复杂的细胞状态,在生物体的整个生命周期中都会发生。通过各种衰老特征,有丝分裂细胞中的细胞衰老已得到明确界定。神经元是具有特殊结构和功能的长寿命有丝分裂后细胞。随着年龄的增长,神经元会出现形态和功能变化,同时伴有蛋白质稳态、氧化还原平衡和钙动力学的改变;然而,这些神经元变化是否属于神经元衰老的特征尚不清楚。在这篇综述中,我们努力识别和分类衰老大脑中神经元相对特有的变化,并通过与常见衰老特征进行比较,将其定义为神经元衰老的特征。我们还将它们与多个细胞稳态系统的功能衰退联系起来,提出这些系统可能是神经元衰老的主要驱动因素。我们希望这一总结将成为进一步探讨神经元衰老综合但相对具体的表型清单的垫脚石,特别是其在衰老过程中潜在的分子事件。这反过来将阐明神经元衰老与神经退行性变之间的联系,并促使人们制定干扰这些过程的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecd2/10529744/3d5c6131a51d/AD-14-5-1618-g1.jpg

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