Age-dependent dysregulation of transcription regulatory machinery triggers modulations in the gene expression levels leading to the decline in cellular fitness. Tracking of these transcripts along the temporal axis in multiple species revealed a spectrum of evolutionarily conserved pathways, such as electron transport chain, translation regulation, DNA repair, etc. Recent shreds of evidence suggest that aging deteriorates the transcription machinery itself, indicating the hidden complexity of the aging transcriptomes. This reinforces the need for devising novel computational methods to view aging through the lens of transcriptomics. Here, we present Homeostatic Divergence Score (HDS) to quantify the extent of messenger RNA (mRNA) homeostasis by assessing the balance between spliced and unspliced mRNA repertoire in single cells. We validated its utility in two independent aging datasets, and identified sets of genes undergoing age-related breakdown of transcriptional homeostasis. Moreover, testing of our method on a subpopulation of human embryonic stem cells revealed a set of differentially processed transcripts segregating these subpopulations. Our preliminary analyses in this direction suggest that mRNA processing level information offered by single-cell RNA sequencing (scRNA-seq) data is a superior determinant of chronological age as compared to transcriptional noise.

转录调控机制的年龄依赖性失调会触发基因表达水平的调节，导致细胞适应性下降。在多个物种中沿时间轴跟踪这些转录本揭示了一系列进化上保守的途径，例如电子传递链、翻译调节、DNA 修复等。 最近的证据表明衰老会破坏转录机制本身，表明隐藏的复杂性老化的转录组。这加强了设计新颖的计算方法以通过转录组学的视角观察衰老的必要性。在这里，我们提出稳态发散评分 (HDS)，通过评估单细胞中剪接和未剪接 mRNA 库之间的平衡来量化信使 RNA (mRNA) 稳态的程度。我们在两个独立的衰老数据集中验证了它的效用，并确定了经历与年龄相关的转录稳态破坏的基因组。此外，在人类胚胎干细胞亚群上测试我们的方法揭示了一组分离这些亚群的差异处理转录本。我们在这个方向上的初步分析表明，与转录噪声相比，单细胞 RNA 测序 (scRNA-seq) 数据提供的 mRNA 加工水平信息是实际年龄的优越决定因素。