小柯机器人

美国加州大学Danica Chen团队近期取得重要工作进展。他们研究发现线粒体未折叠蛋白反应调节海马神经干细胞衰老。相关研究成果2023年5月4日在线发表于《细胞—代谢》杂志上。

据介绍，衰老导致神经干细胞（NSC）、神经发生和认知功能下降，越来越多的证据表明，患有几种神经退行性疾病的患者海马体中的成年神经发生受到干扰。

研究人员对年轻和年老小鼠齿状回的单细胞RNA测序显示，线粒体蛋白折叠应激在神经原性生态位中激活NSC/NPC中很突出，并且随着年龄的增长，伴随着齿状回活化NSC/NPC中细胞周期和线粒体活性的失调而增加。线粒体蛋白折叠应激的增加导致NSC维持受损，齿状回神经发生减少，神经过度活跃和认知功能受损。减少老年小鼠齿状回中线粒体蛋白质折叠应激可以改善神经发生和认知功能。

总之，这些结果证实线粒体蛋白折叠应激是NSC衰老的驱动因素，并提出了改善衰老相关认知能力下降的方法。

附：英文原文

Title: The mitochondrial unfolded protein response regulates hippocampal neural stem cell aging

Author: Chih-Ling Wang, Rika Ohkubo, Wei-Chieh Mu, Wei Chen, Jiang Lan Fan, Zehan Song, Ayane Maruichi, Peter H. Sudmant, Angela O. Pisco, Dena B. Dubal, Na Ji, Danica Chen

Issue&Volume: 2023-05-04

Abstract: Aging results in a decline in neural stem cells (NSCs), neurogenesis, and cognitivefunction, and evidence is emerging to demonstrate disrupted adult neurogenesis inthe hippocampus of patients with several neurodegenerative disorders. Here, single-cellRNA sequencing of the dentate gyrus of young and old mice shows that the mitochondrialprotein folding stress is prominent in activated NSCs/neural progenitors (NPCs) amongthe neurogenic niche, and it increases with aging accompanying dysregulated cell cycleand mitochondrial activity in activated NSCs/NPCs in the dentate gyrus. Increasingmitochondrial protein folding stress results in compromised NSC maintenance and reducedneurogenesis in the dentate gyrus, neural hyperactivity, and impaired cognitive function.Reducing mitochondrial protein folding stress in the dentate gyrus of old mice improvesneurogenesis and cognitive function. These results establish the mitochondrial proteinfolding stress as a driver of NSC aging and suggest approaches to improve aging-associatedcognitive decline.

DOI: 10.1016/j.cmet.2023.04.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00139-0

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