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新陈代谢和蛋白质稳态的变化驱动感觉神经元的衰老表型。

Changes in Metabolism and Proteostasis Drive Aging Phenotype in Sensory Neurons.

作者信息

Kron Nicholas S, Schmale Michael C, Fieber Lynne A

机构信息

Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL, United States.

出版信息

Front Aging Neurosci. 2020 Sep 15;12:573764. doi: 10.3389/fnagi.2020.573764. eCollection 2020.

DOI:10.3389/fnagi.2020.573764
PMID:33101008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7522570/
Abstract

Aging is associated with cognitive declines that originate in impairments of function in the neurons that make up the nervous system. The marine mollusk (Aplysia) is a premier model for the nervous system uniquely suited to investigation of neuronal aging due to uniquely identifiable neurons and molecular techniques available in this model. This study describes the molecular processes associated with aging in two populations of sensory neurons in Aplysia by applying RNA sequencing technology across the aging process (age 6-12 months). Differentially expressed genes clustered into four to five coherent expression patterns across the aging time series in the two neuron populations. Enrichment analysis of functional annotations in these neuron clusters revealed decreased expression of pathways involved in energy metabolism and neuronal signaling, suggesting that metabolic and signaling pathways are intertwined. Furthermore, increased expression of pathways involved in protein processing and translation suggests that proteostatic stress also occurs in aging. Temporal overlap of enrichment for energy metabolism, proteostasis, and neuronal function suggests that cognitive impairments observed in advanced age result from the ramifications of broad declines in energy metabolism.

摘要

衰老与认知能力下降有关,这种下降源于构成神经系统的神经元功能受损。海洋软体动物(海兔)是神经系统的一个主要模型,由于该模型中存在独特可识别的神经元和分子技术,因此特别适合研究神经元衰老。本研究通过在衰老过程(6 - 12个月龄)中应用RNA测序技术,描述了海兔两个感觉神经元群体中与衰老相关的分子过程。在两个神经元群体的衰老时间序列中,差异表达基因聚集成四到五种连贯的表达模式。对这些神经元簇中功能注释的富集分析显示,能量代谢和神经元信号传导相关途径的表达下降,这表明代谢和信号传导途径相互交织。此外,参与蛋白质加工和翻译的途径表达增加,表明蛋白质稳态应激也在衰老过程中发生。能量代谢、蛋白质稳态和神经元功能富集的时间重叠表明,高龄时观察到的认知障碍是能量代谢广泛下降的后果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa3/7522570/14bd2f5bd7bd/fnagi-12-573764-g010.jpg
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