Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging.

Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging.
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DOI:
10.3390/ijms231710032
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发表时间:
2022-09-02
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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背景资料:昼夜节律与衰老过程和性别差异有关;然而,年龄和性别如何改变昼夜节律调节系统仍不清楚。因此,我们的目的是评估基因表达中与年龄和性别相关的变化,并确定可以调节衰老的性别特异性靶分子。研究方法:将大鼠肝脏分为四组,即年轻雄性、老年雄性、年轻雌性和老年雌性,并通过计算机模拟和体外研究证实了参与昼夜节律调节的几个基因的表达。结果如下:基因本体论和京都基因百科全书和基因组途径富集分析表明,在肝脏老化过程中,男性昼夜节律相关基因的表达比女性变化更多。此外,差异表达基因分析和定量实时聚合酶链反应/蛋白质印迹分析显示,Nr 1d 1和Nr 1d 2的表达上调,在男性肝脏老化。此外,其他昼夜节律基因,如Arntl,时钟,Cry 1/2,Per 1/2,和Rora/c的表达,在肝脏衰老过程中男性下降,然而,这些基因在女性肝脏衰老过程中表现出不同的基因表达模式。结论:在肝脏衰老过程中,与Nr 1d 1/2相关的升高下调了男性而非女性的其他昼夜节律基因的表达。因此,与年龄相关的上调Nr 1d 1/2可能发挥更重要的作用,在男性的昼夜节律的变化比女性在肝脏老化。
Background: Circadian rhythm is associated with the aging process and sex differences; however, how age and sex can change circadian regulation systems remains unclear. Thus, we aimed to evaluate age- and sex-related changes in gene expression and identify sex-specific target molecules that can regulate aging. Methods: Rat livers were categorized into four groups, namely, young male, old male, young female, and old female, and the expression of several genes involved in the regulation of the circadian rhythm was confirmed by in silico and in vitro studies. Results: Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the expression of genes related to circadian rhythms changed more in males than in females during liver aging. In addition, differentially expressed gene analysis and quantitative real-time polymerase chain reaction/western blotting analysis revealed that Nr1d1 and Nr1d2 expression was upregulated in males during liver aging. Furthermore, the expression of other circadian genes, such as Arntl, Clock, Cry1/2, Per1/2, and Rora/c, decreased in males during liver aging; however, these genes showed various gene expression patterns in females during liver aging. Conclusions: Age-related elevation of Nr1d1/2 downregulates the expression of other circadian genes in males, but not females, during liver aging. Consequently, age-related upregulation of Nr1d1/2 may play a more crucial role in the change in circadian rhythms in males than in females during liver aging.
DOI: 10.18632/aging.203788
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