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细胞衰老与阿尔茨海默病之间的联系——一篇叙述性综述

Connections Between Cellular Senescence and Alzheimer's Disease-A Narrative Review.

作者信息

Kuźniar Julia, Kozubek Patrycja, Czaja Magdalena, Sitka Hanna, Kochman Urszula, Leszek Jerzy

机构信息

Student Scientific Group of Psychiatry, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.

Department of Psychiatry, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.

出版信息

Int J Mol Sci. 2025 Sep 5;26(17):8638. doi: 10.3390/ijms26178638.

Abstract

Alzheimer's disease, a neurodegenerative brain disorder leading to the progressive decline in cognitive functions, is the most common type of dementia. The main risk factor for its development is aging. Recent studies indicate that cellular senescence mechanisms are among the major factors in a heterogeneous aging process. Cellular senescence is characterized by a permanent proliferative arrest. Many factors might initiate senescence, for example, damage of DNA, shortening of telomeres, dysfunction of mitochondria, and oncogene activation. These processes lead to alterations in the morphology and function of senescent cells. Research is still ongoing to identify one universal marker that could detect senescent cells and distinguish them from other non-proliferating cells. Those cells are involved in age-related pathologies through many heterogeneous processes, including secretion of pro-inflammatory senescence-associated secretory phenotype factors, which affect the brain differently. Alzheimer's disease is an example of a neurodegenerative condition connected to cellular senescence. Senescent cells have been demonstrated to accumulate near Aβ plaques and neurofibrillary tangles. In this review, the multifactorial connection between Alzheimer's disease and cellular senescence is discussed, including topics such as senescence of astrocytes, defective mitochondria, dysregulation of cellular autophagy, and the role of senescent microglia.

摘要

阿尔茨海默病是一种导致认知功能逐渐衰退的神经退行性脑疾病,是最常见的痴呆类型。其发展的主要风险因素是衰老。最近的研究表明,细胞衰老机制是异质性衰老过程中的主要因素之一。细胞衰老的特征是永久性增殖停滞。许多因素可能引发衰老,例如DNA损伤、端粒缩短、线粒体功能障碍和癌基因激活。这些过程导致衰老细胞的形态和功能发生改变。目前仍在进行研究,以确定一种能够检测衰老细胞并将其与其他非增殖细胞区分开来的通用标志物。这些细胞通过许多异质性过程参与与年龄相关的病理过程,包括分泌促炎性衰老相关分泌表型因子,这些因子对大脑的影响各不相同。阿尔茨海默病是与细胞衰老相关的神经退行性疾病的一个例子。衰老细胞已被证明在Aβ斑块和神经原纤维缠结附近积累。在这篇综述中,讨论了阿尔茨海默病与细胞衰老之间的多因素联系,包括星形胶质细胞衰老、线粒体缺陷、细胞自噬失调以及衰老小胶质细胞的作用等主题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40eb/12429568/0822a7f20654/ijms-26-08638-g001.jpg

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