生物钟和进食活动都参与调控外周组织的基因表达节律。钟基因突变以及进食活动的不规律都会引起代谢异常，并影响健康。线粒体参与糖异生、脂肪酸氧化、ATP生产等重要代谢活动。项目组之前发现年青小鼠的肝脏生物钟参与调控线粒体相关基因的表达，并调控线粒体的结构变化、底物利用以及氧化应激水平等的昼夜节律；在年老小鼠肝脏中，钟基因仍有较为正常的表达节律，但线粒体相关基因的表达和氧化应激调控的节律却出现明显紊乱。该结果提示线粒体功能受到生物钟和其它年龄依赖因素的共同调控。在本项申请中，项目组通过mRNA-seq系统比较了年青和年老小鼠肝脏中基因表达水平和节律的差异，发现衰老显著改变了近两百个线粒体相关基因的表达节律，GO分析表明衰老过程中炎症水平的上升以及NAD+水平的下降在其中起到关键作用。HOMER分析显示转录因子X可能是引起相关该变的关键分子。本项目将通过ChIP-seq对相关分析结果进行验证。

Both the circadian clock and feeding can regulate gene expression rhythms in peripheral tissues. Mutations of clock genes and irregular feeding schedules can result in abnormality in metabolism, which is detrimental to health. Mitochondria are involved in critical metabolic processes such as gluconeogenesis, lipid oxidation and ATP production. Our group previously found that the liver clock in young mice regulates the expression of genes related to mitochondrial functions, and rhythms in mitochondrial structural dynamics, substrate utilization and oxidative stress. In old mice, the expression rhythms of clock genes still appear normal. However, several mitochondrial rhythms examined are disrupted. These results suggest that mitochondrial functions are regulated by both the circadian clock and other age-related mechanism(s). In this application, our group used mRNA-seq to systematically compare gene expression level/rhythm in livers of young and old mice, and found that aging altered the expression of more than 200 genes. We used HOMER to analyze the promoter regions of those differential genes and found that transcription factor X is potentially involved in such changes. In addition, GO analyses revealed that increased inflammatory responses and lowering of NAD+ level likely play key roles in age-related changes in gene transcription and expression. We are going to use ChIP-seq to validate the above findings.