||Shuai Ma, Shuhui Sun, Lingling Geng, Moshi Song, Wei Wang, Yanxia Ye, Qianzhao Ji, Zhiran Zou, Si Wang, Xiaojuan He, Wei Li, Concepcion Rodriguez Esteban, Xiao Long, Guoji Guo, Piu Chan, Qi Zhou, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, and Guang-Hui Liu
||Aging causes a functional decline in tissuesthroughout the body that may be delayed by caloricrestriction (CR). However, the cellular profiles andsignatures of aging, as well as those amelioratedby CR, remain unclear. Here, we built comprehen-sive single-cell and single-nucleus transcriptomicatlases across various rat tissues undergoingaging and CR. CR attenuated aging-related changesin cell type composition, gene expression, andcore transcriptional regulatory networks. Immunecells were increased during aging, and CRfavorably reversed the aging-disturbed immuneecosystem. Computational prediction revealed thatthe abnormal cell-cell communication patternsobserved during aging, including the excessiveproinflammatory ligand-receptor interplay, werereversed by CR. Our work provides multi-tissue sin-gle-cell transcriptional landscapes associated withaging and CR in a mammal, enhances our under-standing of the robustness of CR as a geroprotectiveintervention, and uncovers how metabolic interven-tion can act upon the immune system to modify theprocess of aging.