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To investigate the effect of the pathogenic protein amyloid-β (Aβ) on the senescence of human neural stem cells (NSCs), Dr. Li et.al. performed various analyses related to cellular senescence of human NSCs. Senescent phenotypes are significantly increased and accumulated in cell types (microglia, neuron, and so on) associated with Alzheimer’s disease (AD), age-related neurodegenerative disease, and it affects neurogenesis and cognitive function. In this article, we introduce a report that Aβ accelerates cellular senescence by downregulating the expression of SIRT1 protein in human NSCs.
The analysis of cellular senescence was performed by using indicators such as the expression of cell cycle-related genes p16 and p21, senescence-associated β-galactosidase (SA-β-gal) activity, and activation of DNA damage response (expression of γH2AX). SA-β-gal activity was measured by using a fluorescent probe “SPiDER-βGal”. In human NSCs treated with Aβ, it was found that Aβ significantly increased SA-β-gal activity and the expression of p16 and p21. In addition, it was found that Aβ impairs the mitochondrial respiratory chain complexes, resulting in subsequent ROS generation by confirming the increase of mitochondrial ROS and intracellular ROS levels. This suggests that Aβ causes DNA damage by accumulating ROS and accelerated cellular senescence.
Moreover, Aβ treatment reduced the expression of SIRT1 protein, which affects the cellular senescence. When Aβ treatment was performed in human NSCs overexpressed SIRT1, SA-β-gal activity was significantly decreased, and the expression of γH2AX, p16, and p21 was decreased. This suggests that Aβ accelerates cellular senescence by regulating SIRT1. This result also indicated that SIRT1 overexpression may be able to significantly downregulate Aβ-induced cellular senescence in human NSCs.
This report reveals the effect of Aβ on human NSCs senescence, which is rarely studied. These findings suggest that SIRT1 is a highly promising therapeutic target for anti-aging in human NSCs. Accordingly, studying the treatment strategies for age-related neurodegenerative disorders such as Alzheimer’s disease will continue to develop.
Rongyao Li, Yi Li, Haowei Zuo, Gang Pei, Shichao Huang and Yujun Hou, “Alzheimer’s Amyloid-β Accelerates Cell Senescence and Suppresses SIRT1 in Human Neural Stem Cells”, Biomolecules, 2024, 14, 189. doi: 10.3390/biom14020189
Special thanks to our partner Ms. Yasuka Komatsu from Dojindo Laboratories, JAPAN, for writing this article.
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