aCentre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW AustraliabNeuropsychiatric Institute, Prince of Wales Hospital, SydneycDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
Curr Opin Psychiatry. 2016 Mar;29(2):159-67. doi: 10.1097/YCO.0000000000000238.
The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain.
Profiling 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.
Gene 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.
本文旨在总结近年来人类大脑衰老过程中基因表达研究的最新进展。
对正常衰老过程中人类大脑中差异表达基因或“转录本”的分析，为了解在老年期被激活或抑制的生物学途径提供了有价值的见解。介导神经炎症和免疫系统激活的基因表现出明显的与年龄相关的上调，使衰老大脑易患神经退行性和神经精神疾病。细胞离子失衡和多种分子对突触效能的影响与晚年的神经认知能力下降有关。至关重要的是，这些研究还揭示了衰老人类大脑中保护性遗传反应的动员情况，有助于确定老年期的健康和疾病轨迹。人们对转录前和转录后基因表达调控因子的研究，特别是非编码 RNA 的作用，产生了越来越大的兴趣，因为它们是导致人类大脑衰老表型多样性的介导因素。
健康大脑衰老的基因表达研究为揭示神经认知衰老以及晚年疾病风险和恢复能力的复杂调节细胞基础提供了机会。这样，就可以研究针对与年龄相关的神经退行性疾病的早期干预新途径，这可能对开发疾病修饰疗法具有重要意义。
