Department of Electrical Engineering, Stanford University, Palo Alto, United States.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, United States.
Elife. 2021 Apr 13;10:e62293. doi: 10.7554/eLife.62293.
Aging is associated with complex molecular and cellular processes that are poorly understood. Here we leveraged the Tabula Muris Senis single-cell RNA-seq data set to systematically characterize gene expression changes during aging across diverse cell types in the mouse. We identified aging-dependent genes in 76 tissue-cell types from 23 tissues and characterized both shared and tissue-cell-specific aging behaviors. We found that the aging-related genes shared by multiple tissue-cell types also change their expression congruently in the same direction during aging in most tissue-cell types, suggesting a coordinated global aging behavior at the organismal level. Scoring cells based on these shared aging genes allowed us to contrast the aging status of different tissues and cell types from a transcriptomic perspective. In addition, we identified genes that exhibit age-related expression changes specific to each functional category of tissue-cell types. Altogether, our analyses provide one of the most comprehensive and systematic characterizations of the molecular signatures of aging across diverse tissue-cell types in a mammalian system.
衰老是与复杂的分子和细胞过程相关联的，这些过程我们还不甚了解。在这里，我们利用 Tabula Muris Senis 单细胞 RNA-seq 数据集，系统地描述了在小鼠的不同组织细胞类型中衰老过程中的基因表达变化。我们在 23 种组织中的 76 种组织细胞类型中鉴定出了与衰老相关的基因，并描述了共享和组织细胞特异性的衰老行为。我们发现，在多种组织细胞类型中共享的与衰老相关的基因，在大多数组织细胞类型中，随着衰老其表达也会朝着相同的方向一致变化，这表明在机体水平上存在着协调一致的整体衰老行为。基于这些共享的衰老基因对细胞进行评分，使我们能够从转录组学的角度对比不同组织和细胞类型的衰老状态。此外，我们还鉴定出了在每个组织细胞类型的功能类别中表现出与年龄相关的表达变化的基因。总的来说，我们的分析提供了哺乳动物系统中不同组织细胞类型衰老的分子特征的最全面和系统的描述之一。
