Study on caloric restriction delaying aging by regulating key rhythmic genes in the liver
ZHANG Kaige
YANG Qian
Abstract：Objective To explore the role of rhythmic genes in liver tissue in delaying aging through caloric restriction(CR)by analyzing sequencing data from public databases.Methods RNA sequencing(RNA-seq)and assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)original sequencing data were downloaded from the GEO database,including samples from liver tissues of 4-month-old young mice,24-month-old aged mice,and 24-month-old aged mice under CR.A list of rhythmic liver genes was obtained from the CGDB database.Differentially expressed gene analysis,differential chromatin accessibility analysis,functional enrichment analysis,integrated RNA-seq and ATAC-seq analysis,and transcription factor prediction were performed.Results For RNA-seq data,by comparing the aged group with the young group and the CR group with the aged group,305 genes(upregulated during aging,downregulated under CR)and 565 genes(downregulated during aging,upregulated under CR)were identified,which showed significant changes during aging that could be reversed by CR.Functional enrichment analysis revealed that these genes were mainly involved in rhythmic processes such as circadian rhythm regulation and autophagy.Core clock genes such as Nr1d1,Cry2,and important rhythmic genes like Gsk3b and Mtor,which were significantly downregulated during aging,were found to be upregulated under CR.For ATAC-seq data,functional enrichment of genes annotated to differential accessible chromatin regions during aging and under CR conditions indicated significant enrichment in circadian rhythm regulation pathways.Combined analysis of transcriptomic and chromatin accessibility data identified genes with significant changes in both chromatin accessibility and expression,including key rhythmic genes like Mtor and Rorc.Subsequently,potential transcription factors regulating these differentially expressed genes were predicted using homer software.Conclusion This study systematically assessed the crucial role of rhythmic genes in delaying aging through CR by analyzing public database data,identifying key genes such as Nr1d1,Cry2,Gsk3b,and Mtor.It provides new perspectives and data support for a deeper understanding of the mechanisms by which CR delays aging and offers potential targets for anti-aging interventions.
Keywords：agingcaloric restrictionRNA sequencingassay for transposase-accessible chromatin with high-throughput sequencingrhythmic genetranscription factor
Publication Date：2025-02-27
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 214-221 )