Transcriptomic Atlas Of Liver Aging

With the widespread aging of the population,aging research has gradually become one of the research hotspots in the medical field.More and more basic research and epidemiological investigations have shown that aging will cause the gradual damage to the homeostasis of the genome,cells,tissues and the entire organism,which in turn reduces survival and reproduction,and increases the risk of disease and death.Past studies have confirmed the nine hallmarks of aging at the cellular level,including genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,deregulated nutrient-sensing,mitochondrial dysfunction,cellular senescence,stem cell exhaustion and altered intercellular communication.Various experimental interventions to slow down and partially reverse aging,such as caloric restriction,have also been proposed.Compared with other aging organs,the liver seems to be a rare organ in the body that can challenge the aging process,but it still inevitably appears changes in structure and function during the aging process,such as volume reduction,reduced blood flow,changes in appearance,and decreased metabolic and regeneration capabilities.And these changes have an important impact on the aging process of other human organs and disease susceptibility.Therefore,an accurate understanding of the mechanisms behind liver aging can more effectively develop aging interventions and anti-aging drugs,thereby improving the quality of life of the elderly and reducing the incidence and mortality of liver diseases.In previous studies of liver aging,researchers have reported multiple messengerRNAs related to aging by analyzing the whole genome transcriptome of humans and other mammals.In addition,aging-related epigenetic changes have also been shown to affect gene expression,resulting in messengerRNA and various non-codingRNAs participating in the changes in aging phenotype.However,due to the difficulty of clinical sample collection and the high cost of sequencing,these studies have mainly focused on aging livers in animal models such as mice.Even if the research is based on the human liver,the research goals are mostly related to diseases or damages such as fibrosis,cancer and diabetes,which shows that there is still a lack of research on the natural aging changes of the liver.Therefore,in this study,we collected 9 samples of healthy liver from transplantation donors which were transferred to the whole transcriptome sequencing and analyzed these transcriptional expression change at the messengerRNA(mRNA),long non-codingRNA(lncRNA),and microRNA(miRNA)levels.And a competitive endogenousRNA(ceRNA)regulatory network including the three is proposed,highlighting the important effect of ncRNAs,such as mi R-10b-5p,mi R-450b-5p,mi R-6087,FAM30 A,LINC01447.To ensure its reliability,we performed real-time fluorescence quantitative reverse transcription polymerase chain reaction(q RT-PCR)for verification on the liver samples of another 11 patients with benign liver diseases,which proved that the sequencing data and its results are consistent.And using the sequencing data of more healthy liver samples from the Genotype-Tissue Expression(GTEx)database,the weighted correlation network analysis(WGCNA)was performed,which confirmed the extensive changes in immune and extracellular matrix-related pathways during the aging process.In addition,we also used the public datasets in the Gene Expression Omnibus(GEO)database to explore the genetic changes and cell state changes of liver aging at the single-cell level.Finally,based on the above results,this study has obtained complete transcriptomic atlas of liver natural aging,which provides a reliable transcriptomic theoretical basis for subsequent liver aging research.