Chen Jianning, Zou Qin, Lv Daojun, Raza Muhammad Ali, Wang Xue, Chen Yan, Xi Xiaoyu, Li Peilin, Wen Anxiang, Zhu Li, Tang Guoqing, Li Mingzhou, Li Xuewei, Jiang Yanzhi
Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan, China.
Sichuan Weimu Modern Agricultural Science and Technology Co., Ltd, Chengdu, Sichuan, China.
PeerJ. 2019 May 17;7:e6949. doi: 10.7717/peerj.6949. eCollection 2019.
Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging.
In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes.
A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging.
Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.
衰老为多种疾病发生的主要风险因素，肝脏作为最重要的代谢器官，受到衰老的显著影响。研究表明，啮齿动物肝脏重量随年龄增长往往增加，而人类肝脏重量则随年龄增长而减少。猪具有与人类相似的基因组结构、生理及生化特征，因此被用作研究人类疾病的重要模型。大型哺乳动物肝脏衰老在全面转录水平上的分子机制仍知之甚少。猪是清晰且全面理解人类肝脏衰老潜在分子机制的理想模式动物。
本研究中，对4头健康的中国本土雅南猪雌性猪进行了研究：2头年轻母猪（180日龄）和2头老年母猪（8岁）。采用高通量RNA测序技术评估猪肝脏衰老过程中信使RNA、长链非编码RNA、微小RNA和环状RNA的表达谱。进行基因本体（GO）分析以研究与年龄相关基因的生物学功能。
在猪肝脏中鉴定出许多与年龄相关的基因。GO注释显示，上调基因主要与免疫反应相关，而下调基因主要与代谢相关。此外，还发现一些长链非编码RNA及其靶基因在肝脏衰老过程中差异表达。此外，在肝脏衰老过程中评估了多组协同控制关系并构建了环状RNA-微小RNA共表达网络。
鉴定出众多与年龄相关的基因，并构建了猪肝脏衰老过程中活跃的环状RNA-微小RNA共表达网络。这些发现有助于理解肝脏衰老的转录基础，也为在分子水平阐明人类肝脏衰老提供了进一步的参考。
