The molecular characteristics of aging that lead to increased disease susceptibility remain poorly understood. Here we present a transcriptomic profile of the human brain associated with age and aging, derived from a systematic integrative analysis of four independent cohorts of genome-wide expression data from 2202 brain samples (cortex, hippocampus and cerebellum) of individuals of different ages (from young infants, 5-10 years old, to elderly people, up to 100 years old) categorized in age stages by decades. The study provides a signature of 1148 genes detected in cortex, 874 genes in hippocampus and 657 genes in cerebellum, that present significant differential expression changes with age according to a robust gamma rank correlation profiling. The signatures show a significant large overlap of 258 genes between cortex and hippocampus, and 63 common genes between the three brain regions. Focusing on cortex, functional enrichment analysis and cell-type analysis provided biological insight about the aging signature. Response to stress and immune response were up-regulated functions. Synapse, neurotransmission and calcium signaling were down-regulated functions. Cell analysis, derived from single-cell data, disclosed an increase of neuronal activity in the young stages of life and a decline of such activity in the old stages. A regulatory analysis identified the transcription factors (TF) associated with the signature of 258 genes, common to cortex and hippocampus; revealing the role of MEF2(A,D), PDX1, FOSL(1,2) and RFX(5,1) as candidate regulators of the signature. Finally, a deep-learning neural network algorithm was used to build a biological age predictor based on the aging signature. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.

中文翻译：

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转录组学景观，基因特征和人脑衰老的调控特征。

导致疾病易感性增加的衰老分子特征仍然知之甚少。在这里，我们呈现了与年龄和衰老相关的人类大脑的转录组图谱，其来源于对来自不同年龄（来自）的2202个大脑样本（皮层，海马和小脑）的四个独立的全基因组表达数据队列的系统综合分析5至10岁的小婴儿至100岁以下的老年人）按年龄划分了数十年。这项研究提供了一个特征，即在皮质中检测到1148个基因，在海马中检测到874个基因，在小脑中检测到657个基因，根据稳健的γ秩相关分析，这些表达随年龄呈现显着差异。签名显示，皮层和海马之间的258个基因有很大的重叠，三个大脑区域之间共有63个共同基因。专注于皮层，功能富集分析和细胞类型分析提供了有关衰老特征的生物学见解。对压力的反应和免疫反应是上调的功能。突触，神经传递和钙信号转导下调功能。从单细胞数据得出的细胞分析显示，在生命的年轻阶段神经元活动增加，而在老年阶段神经活动减少。监管分析确定了与皮层和海马共有的258个基因的签名相关的转录因子（TF）。揭示了MEF2（A，D），PDX1，FOSL（1,2）和RFX（5,1）作为签名候选调节器的作用。最后，深度学习神经网络算法用于基于衰老签名构建生物年龄预测因子。本文是由Federico Manuel Giorgi博士和Shaun Mahony博士编辑的题为：转录谱和调控基因网络的特刊的一部分。