Neuronal Senescence in the Aged Brain.
Neuronal Senescence in the Aged Brain.
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DOI：
10.14336/ad.2023.0214
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发表时间：
2023-10-01
影响因子：
7.4
通讯作者：
Chong, Cheong-Meng
中科院分区：
文献类型：
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作者：
Chou, Shu-Min;Yen, Yu-Hsin;Yuan, Fang;Zhang, Su-Chun;Chong, Cheong-Meng
细胞衰老是一种高度复杂的细胞状态，发生在生物体的整个生命周期中。它在有丝分裂细胞中通过各种衰老特征被很好地定义。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，神经元显示形态和功能的变化，伴随着蛋白质稳态，氧化还原平衡和Ca2+动力学的改变，但是，它是模糊的，这些神经元的变化是否属于神经元衰老的功能。在这篇综述中，我们努力识别和分类的变化是相对具体的神经元在老化的大脑，并定义为神经元衰老的功能，通过与常见的衰老功能比较。我们还将它们与多个细胞内稳态系统的功能下降相关联，提出这些系统是神经元衰老的主要驱动因素的可能性。我们希望这一总结将作为一个垫脚石，进一步输入一个全面的，但相对具体的表型神经元衰老，特别是其潜在的分子事件在老化过程中的列表。这将反过来照亮神经元衰老和神经退行性变之间的关联，并导致开发干扰该过程的策略。
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 Ca2+ 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.