Department of Biological, Geological, and Environmental Sciences and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH, 44115, USA.
Sci Rep. 2017 Aug 29;7(1):9716. doi: 10.1038/s41598-017-09289-9.
The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. Many physiological effects of CR differ between males and females; here we investigated if the sex of animals affects the CR induced changes in the circadian rhythms. The liver expression of some circadian clock genes such as Bmal1 and three Periods (Per1, Per2 and Per3) and the effect of CR on the expression of these genes were sex independent, while the expression of Rev-Erb alpha, Ror gamma and both Cryptochome (Cry1 and Cry2) genes was different between males and females. The effect of CR on Rev-Erb alpha, Ror gamma and Cry1 gene expression was sex dependent. The expression and the effects of CR were sex-specific for several genes previously reported to be regulated by CR: Fmo3, Mup4, Serpina12 and Cyp4a12, while the expression of Cyp4a14a was sex independent. IGF signaling plays an important role in aging and CR effects. Igf-1 expression is regulated by CR and by the circadian clock, we found that rhythms in Igf-1 expression have sexual dimorphism. Our data provide molecular evidence that the sex of animals is an important modulator of circadian rhythms in gene expression and their response to CR.
生物钟基因表达的节律受到热量限制（CR）的影响，CR 是一种已知能延长寿命的饮食模式。CR 的许多生理效应在男性和女性之间存在差异；在这里，我们研究了动物的性别是否会影响 CR 诱导的生物钟节律变化。一些生物钟基因，如 Bmal1 和三个 Periods（Per1、Per2 和 Per3）在肝脏中的表达以及 CR 对这些基因表达的影响与性别无关，而 Rev-Erb alpha、Ror gamma 和两个 Cryptochome（Cry1 和 Cry2）基因的表达在男性和女性之间存在差异。CR 对 Rev-Erb alpha、Ror gamma 和 Cry1 基因表达的影响具有性别依赖性。先前报道的一些受 CR 调节的基因的表达和 CR 的影响具有性别特异性：Fmo3、Mup4、Serpina12 和 Cyp4a12，而 Cyp4a14a 的表达与性别无关。IGF 信号在衰老和 CR 效应中发挥重要作用。IGF-1 的表达受 CR 和生物钟的调节，我们发现 IGF-1 表达的节律存在性别二态性。我们的数据提供了分子证据，表明动物的性别是基因表达及其对 CR 反应的生物钟节律的重要调节因素。
