卡路里限制通过调节肝脏关键节律基因延缓衰老的研究  

Study on caloric restriction delaying aging by regulating key rhythmic genes in the liver

作　　者：张凯歌 杨倩 ZHANG Kaige;YANG Qian(Department of Experimental Surgery,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China)

机构地区：[1]空军军医大学唐都医院实验外科,陕西西安710038

出　　处：《空军军医大学学报》2025年第2期214-221,共8页Journal of Air Force Medical University

基　　金：国家自然科学基金(31930048,82221001);空军军医大学“凌云工程”个人项目(2020lyjhyq)。

摘　　要：目的 通过分析公共数据库测序数据,探究肝脏组织中节律基因在卡路里限制(CR)延缓衰老中的作用。方法 从GEO数据库中下载来自小鼠肝脏组织4月龄年轻组、24月龄衰老组和24月龄CR衰老组样本的转录组测序(RNA-seq)和染色质可及性测序(ATAC-seq)原始测序数据,从CGDB数据库中下载整理肝脏节律基因列表。并进行差异表达基因分析、差异染色质开放区域分析、功能富集分析、RNA-seq和ATAC-seq联合分析以及转录因子预测。结果 针对RNA-seq数据,通过将衰老组与年轻组以及CR组与衰老组比较,得到衰老时的显著变化可被CR所逆转的基因,分别有305个(衰老时上调,CR处理下调)和565个(衰老时下调,CR处理上调),功能富集结果显示这些基因主要参与了昼夜节律调控、自噬等节律过程,其中包含有核心生物钟基因Nr1d1、Cry2以及重要节律基因Gsk3b和Mtor,其表达在衰老时出现显著下调,CR可显著上调这种变化。对于ATAC-seq数据,分别将衰老时以及CR条件下的差异染色质开放区域注释基因进行功能富集,结果显示这些基因显著富集于昼夜节律调控相关通路,并联合转录组分析,结果为染色质可及性和基因表达均显著变化,其中包括有Mtor和Rorc等重要节律基因,接着使用homer软件预测出潜在调控其差异表达的转录因子。结论 本文通过公共数据库分析的方法,系统评估了节律基因在CR延缓衰老中的重要作用,并鉴定出其中的关键基因如Nr1d1、Cry2、Gsk3b和Mtor等。为更深入理解CR延缓衰老的机制提供了新的视角和数据支撑,并为抗衰老提供了潜在的靶点。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 throu

关 键 词：衰老 卡路里限制 转录组测序 染色质可及性测序 节律基因 转录因子 

分 类 号：R394[医药卫生—医学遗传学]