衰老过程中行为和认知功能退化的调控机制研究

doi:10.16288/j.yczz.21-060

遗传 ›› 2021, Vol. 43 ›› Issue (6): 545-570.doi: 10.16288/j.yczz.21-060

衰老过程中行为和认知功能退化的调控机制研究

袁洁^1,²(), 蔡时青^1,²

1. 中国科学院神经科学研究所,神经科学国家重点实验室,上海 200031
2. 中国科学院脑科学与智能技术卓越创新中心,上海 200031

收稿日期:2021-02-08 修回日期:2021-03-11 出版日期:2021-06-20 发布日期:2021-03-30
通讯作者: 袁洁 E-mail:yuanjiejane@gmail.com
作者简介:袁洁,2010年毕业于华中科技大学生命科学与技术学院,获理学学士学位。2010—2018年就读于中国科学院大学,在神经科学研究所离子通道调控研究组攻读博士学位,导师为蔡时青研究员。目前在美国约翰霍普金斯大学接受博士后训练。博士期间主要探究健康衰老的调控机制。通过全基因组RNAi筛选,找到一系列调控衰老相关行为退化的候选基因,揭示了新的神经系统衰老的基因调控网络;从中鉴定了两个全新的抗衰老基因靶标,并详细阐明了它们以及它们在哺乳动物中的同源基因在衰老相关行为和认知功能退化中的作用,为如何实现健康衰老提供了全新的线索;此外,还揭示了表观遗传抑制线粒体功能在衰老大脑和神经退行性疾病发生和发展中发挥重要作用,为老年性疾病的干预方法开发提供了方向。博士论文《表观遗传调控因子BAZ-2和SET-6调节衰老的机制研究》获得2020年中国科学院优秀博士学位论文。
基金资助:
国家自然科学基金项目资助编号(91949206)

The regulatory mechanisms of behavioral and cognitive aging

Jie Yuan^1,²(), Shiqing Cai^1,²

1. Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China
2. CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China

Received:2021-02-08 Revised:2021-03-11 Online:2021-06-20 Published:2021-03-30
Contact: Yuan Jie E-mail:yuanjiejane@gmail.com
Supported by:
Supported by the National Natural Science Foundation of China No(91949206)

摘要/Abstract

摘要：

随着人类预期寿命延长,人口老龄化问题越来越严重。过去几十年关于衰老的研究使人们对长寿的生物学机理有了一定的认识,然而延长寿命应以保持老年个体健康的行为和认知功能为前提,近期研究显示延长寿命不一定延缓衰老过程中的行为和认知功能退化。衰老相关行为退化的调控机制目前知道的还很少,如何实现老年人口健康的衰老是现代社会极具挑战也是迫切需要解决的问题。衰老过程伴随着明显的认知等行为功能的退化,过去的研究对这些功能的退化进行了比较详细的描述,包括情节记忆、工作记忆、信息处理速度等认知功能的衰退,运动能力降低,节律紊乱等。随着神经科学与技术的发展,越来越多的研究集中到大脑的结构和功能随衰老的改变。本文在简单描述衰老过程中行为功能退化现象的基础上,主要对大脑结构和网络连接、神经元形态和功能、大脑基因表达以及一些保守的生物学信号通路等方面在衰老过程中的改变的研究进展展开综述性介绍,重点关注这些变化与行为和认知功能退化之间的联系。目前大部分的研究结果还只建立了这些变化与行为和认知功能退化的相关关系,因果关系的确立还有待进一步的研究。相信更多对衰老过程中行为和认知功能退化的调控机制的研究将对改善老年人的生活质量有极大帮助,同时对寻找预防神经退行性疾病发生的方法也有指示作用。

关键词: 衰老, 认知功能, 行为退化, 突触, 神经递质, 线粒体, 氧化压力, 表观遗传

Abstract:

With the increase of life expectancy, the world’s population is aging rapidly. Previous work in the field of aging greatly increases our understanding of biological mechanisms underlying longevity. Researchers have unraveled a number of longevity pathways conserved from yeast to mammals. However, recent evidence shows that mechanisms regulating the life span and those regulating age-related behavioral decline could be dissociated. The regulatory mechanisms underlying behavioral and cognitive aging is largely unknown. Previous work has described a significant age-related decline in cognitive behaviors including episodic memory, working memory, processing speed, as well as motor function deterioration and circadian dysfunction. With the advance of neuroscience and technology, more and more studies have focused on the age-related changes in structure and function of the brain. In this review, we briefly describe the deterioration of cognitive function and other behaviors in the aging process, and survey the role of age-related changes in brain structure and network, neuron morphology and function, transcriptome in brain and some conserved biological pathways on age-related cognitive and behavioral decline. Further studies on the mechanisms underpinning age-related cognitive and behavioral decline may provide clues not only for improving the quality of life for the ageing population, but also for developing intervention approaches for neurodegenerative diseases.

Key words: aging, cognitive function, behavioral deterioration, synapse, neurotransmitter, mitochondrion, oxidative stress, epigenetic

袁洁, 蔡时青. 衰老过程中行为和认知功能退化的调控机制研究[J]. 遗传, 2021, 43(6): 545-570.

Jie Yuan, Shiqing Cai. The regulatory mechanisms of behavioral and cognitive aging[J]. Hereditas(Beijing), 2021, 43(6): 545-570.

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衰老过程中行为和认知功能退化的调控机制研究

The regulatory mechanisms of behavioral and cognitive aging

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