Transcriptome analysis of synaptosomes in ageing

An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between transcriptome and proteome at soma and synaptic level during aging. Proteomic and transcriptomic data analysis reveal that, in young animals, proteins and transcripts are correlated and synaptic regulation is driven by changes in the soma. During aging, there is a decoupling between transcripts and proteins and between somatic and synaptic compartments. Furthermore, soma-synapse gradient of ribosomal genes changes upon aging, i.e. ribosomal transcripts are less abundant and ribosomal proteins are more abundant in synaptic compartment of old mice with respect to younglings. Additionally, transcriptomics data highlight a difference in the splicing of certain synaptic mRNA with aging. Taken together, our data provide a valuable resource for the study of the aging synapse. 32 samples: age: 3w, 5m, 18m, 19m; conditions: 2 per age group (SG/TH); biol. Replicates per age group and condition: 4衰老的核心标志性特征之一为蛋白稳态（proteostasis）丧失，该现象可引发神经元内蛋白质聚集与线粒体功能障碍。尽管学界已证实，大脑内蛋白质合成受到精密调控，尤其在突触位点——信使RNA（mRNA）可通过活动依赖的方式完成局部翻译，但目前针对衰老过程中突触蛋白质组（synaptic proteome）与转录组（transcriptome）的变化规律，相关研究仍较为匮乏。因此，本研究旨在阐明衰老过程中胞体（soma）与突触水平上，转录组与蛋白质组之间的调控关联。蛋白质组学与转录组学数据分析结果显示：在年轻个体体内，蛋白质与转录本呈现显著相关性，且突触调控主要由胞体层面的变化所驱动。而在衰老过程中，转录本与蛋白质之间、胞体与突触区室（synaptic compartment）之间均出现解偶联现象。此外，核糖体基因的胞体-突触梯度分布会随衰老发生显著改变：相较于年轻小鼠，老年小鼠突触区室内的核糖体转录本丰度显著降低，而核糖体蛋白质的丰度则显著升高。除此之外，转录组学数据还显示，部分突触mRNA的剪接模式会随衰老进程出现特异性差异。综上，本研究产生的数据集可为衰老突触的相关研究提供极具价值的参考资源。本次数据集共包含32个样本：样本年龄分为3周、5月龄、18月龄、19月龄四组；每组年龄对应两种实验条件（SG/TH）；每个年龄组与实验条件下均设置4个生物学重复。