Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging
Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging
复制标题
热量限制重新编程褐家鼠衰老的单细胞转录景观
DOI：
10.1016/j.cell.2020.02.008
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发表时间：
2020-03-05
期刊：
影响因子：
64.5
通讯作者：
Liu, Guang-Hui
中科院分区：
文献类型：
--
作者：
Ma, Shuai;Sun, Shuhui;Liu, Guang-Hui
衰老会导致整个人体组织的功能下降，这可能会因热量限制（CR）延迟。然而，衰老的细胞谱和特征以及CR改善的细胞特征和特征尚不清楚。在这里，我们在经历衰老和CR的各种大鼠组织中建立了全面的单细胞和单核转录图。细胞类型组成，基因表达和核心转录调节网络的衰老相关变化减弱。在衰老过程中，免疫细胞增加，CR可逆转衰老的衰老免疫生态系统。计算预测表明，在衰老过程中观察到的异常细胞 - 细胞通信模式，包括过度促炎配体 - 受体相互作用，被CR逆转。我们的工作提供了与哺乳动物衰老和CR相关的多组织单细胞转录景观，从而增强了我们对CR作为老年保护干预的鲁棒性的理解，并揭示了代谢干预如何在免疫系统上起作用以修改衰老过程。
Aging causes a functional decline in tissues throughout the body that may be delayed by caloric restriction (CR). However, the cellular profiles and signatures of aging, as well as those ameliorated by CR, remain unclear. Here, we built comprehensive single-cell and single-nucleus transcriptomic atlases across various rat tissues undergoing aging and CR. CR attenuated aging-related changes in cell type composition, gene expression, and core transcriptional regulatory networks. Immune cells were increased during aging, and CR favorably reversed the aging-disturbed immune ecosystem. Computational prediction revealed that the abnormal cell-cell communication patterns observed during aging, including the excessive proinflammatory ligand-receptor interplay, were reversed by CR. Our work provides multi-tissue single-cell transcriptional landscapes associated with aging and CR in a mammal, enhances our understanding of the robustness of CR as a geroprotective intervention, and uncovers how metabolic intervention can act upon the immune system to modify the process of aging.