Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Sci Rep. 2017 Jul 19;7(1):5894. doi: 10.1038/s41598-017-05927-4.
It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations. In addition, 113 biological processes, including neuronal and synaptic functions, were consistently associated with genes showing an up-down tendency among all datasets. Genes up-regulated during in vitro neuronal differentiation also displayed a tendency for up-down reversal, although at levels comparable to other genes. We argue that reversals may not represent aging-related neuronal loss. Instead, expression reversals may be associated with aging-related accumulation of stochastic effects that lead to loss of functional and structural identity in neurons.
先前有报道称，老年人前额叶皮层的 mRNA 表达水平开始类似于成年前的水平。这种表达的逆转可能意味着衰老大脑中细胞身份的丧失，并为与衰老相关的分子变化和功能下降之间提供了联系。在这里，我们分析了 19 个大脑转录组年龄系列数据集，包括 17 个不同的大脑区域，以研究人类大脑中表达逆转的普遍性和功能特性。在所有 19 个数据集，25 个基因在出生后发育过程中持续上调，并在衰老过程中下调，表现出一种“上升-下降”的模式，这是通过随机排列确定的显著模式。此外，113 个生物学过程，包括神经元和突触功能，与所有数据集都显示出上升-下降趋势的基因始终相关。在体外神经元分化过程中上调的基因也表现出上升-下降逆转的趋势，尽管水平与其他基因相当。我们认为，逆转可能不代表与衰老相关的神经元丧失。相反，表达的逆转可能与衰老相关的随机效应积累有关，这些效应导致神经元的功能和结构丧失。
