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Dysregulation of macroautophagy/autophagy has been closely implicated in aging. Caloric restriction (CR) is an effective intervention of aging partially via activation of autophagy. Recently, a high-throughput single-cell RNA-seq technique has been employed to detect the comprehensive transcriptomes of individual cells. However, the transcriptional networks of  ATG  (autophagy related) genes in the aging process and the modulation of  ATG  genes expression by CR at the single-cell level have not been elucidated. Here, by performing data analysis of single nucleus/cells RNA sequencing in rats undergoing aging and the modulation by CR, we demonstrate that the transcription patterns of  Atg  genes in different cell types of rat liver, brain, and kidney are highly heterogeneous. Importantly, CR reversed aging-induced changes of multiple  Atg  genes across different cell types in the brain, liver, and kidney. In summary, our results, for the first time, provide comprehensive information on  Atg  gene expression in specific cell types of different organs in a mammal during aging and give novel insight into the protective role of autophagy and CR in aging at the single-cell resolution. Abbreviations:ATG  genes: autophagy-related genes;  Atg5 : autophagy related 5;  Atg7 : autophagy related 7; CR: caloric restriction; DEATG: differentially expressed autophagy-related; NAFLD: nonalcoholic fatty liver disease; ScRNA-seq: single-cell RNA sequencing

Modulation of Atg genes expression in aged rat liver, brain, and kidney by caloric restriction analyzed via single-nucleus/cell RNA sequencing