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Gene expression in the aging human brain: an overview

机译:人类衰老的大脑中的基因表达:概述

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摘要

Purpose of reviewThe review aims to provide a summary of recent developments in the study of gene expression in the aging human brain.Recent findingsProfiling differentially expressed genes or transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging.SummaryGene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.
机译:审查目的本综述旨在概述衰老人脑中基因表达研究的最新进展最新发现分析正常衰老过程中人脑中差异表达的基因或转录本为生物学途径提供了宝贵的见解在晚年似乎被激活或抑制。尤其是介导神经炎症和免疫系统激活的基因显示出明显的与年龄相关的上调,从而在衰老的大脑中形成了对神经退行性疾病和神经精神疾病的脆弱状态。细胞离子动态失衡和与年龄有关的大量对突触功效的分子影响可能是晚年神经认知功能下降的基础。至关重要的是,这些研究还揭示了人脑老化过程中保护性遗传反应的动员,这些反应有助于确定老年人的健康和疾病轨迹。对基因表达的转录前和转录后调控子的研究日益引起人们的兴趣,尤其是非编码RNA作为表征人脑衰老的表型多样性的介体的作用。总结基因表达研究在健康的脑衰老中提供了一个机会来阐明神经认知衰老以及疾病风险和晚年适应能力的复杂调控的细胞基础。这样,可以研究与年龄相关的神经退行性疾病的早期干预的新途径,这对疾病改良疗法的发展具有潜在的重大意义。

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