| Objects:The longevity and ageing of humans are controlled by hereditary factors,the gene expression profiles are different between ageing and youth,longevity family individuals and non-longevity individuals.The aim is to distinguish the longevity-or ageing differential expression genes(DEGs).Gene expression is regulated by epigenetic modification,and DNA methylation is one of the epigenetic modification patterns and dynamically changed by environmental factors,it is related to human longevity,ageing,disease onset and procedure.According to these clues and focusing on the gene regulation,the study aims to distinguish longevity differential methylation CpG sites and genes based on the longevity people from Guangxi followed by detecting the methylation profile in the promoter region of NFATC1 in order to explore the relationship of DNA methylation and human longevity.Methods:?WGCNA was conducted to analyze the dataset GSE16717 on the GEO to distinguish the longevity-or ageing differential expression genes(DEGs).The expression profiles of specific ageing DEGs CCR6 and ID3 were detected in the population.?The DNA methylation chip array was conducted on the population from Guangxi Bama region who was grouped into longevity family group and non-longevity family group.The longevity differential methylation Cp G sites and genes were detected.Another study with longevity,longevity`s offspring and non-longevity family group was built to exam the methylation profile in promoter region of NFATC1.Results:?296 longevity DEGs were recognized and negaitively expressed with lifespan which involved in GO:0005634~nucleus,T cell receptor signaling pathways.The top 10 specific longevity DEGs were CAMK4,SLC16A10,EPHA4,TAMM41,MAN1C1,DPH1,SIT1,GMPS,PRRC2 B,DEXI.46 ageing DEGs were recognized and negaitively expressed with age which involved in GO:0042113~B cell activation and hsa04662: B cell receptor signaling pathways.The top 10 specific ageing DEGs were CR2,VREB3,ID3,MS4A1,TCL1 A,CCR6,OSBPL10,USPL1,HS3ST1,SPIB.?The expression profiles of specific ageing DEGs CCR6 and ID3 were significantly different(under 74 yrs > 75 yrs and above)and negatively correlated to age.?NFATC1?SHC2?ULBP1?CD37?IL11 hyper methylated,and MAPK3?PIK3R5?CORO1A?AKT1,PRKCZ hypo methylated in the longevity family individuals.?The methylation profile on chr77157891 in the promoter region of NFATC1 gene was significantly different(longevity > non longevity family group,longevity`s offspring>non longevity family group).The methylation profile on chr77157909 was significantly different(longevity < longevity`s offspring,longevity<non longevity family group),it was also different between gender of the longevity offspring and non-longevity family group(female<male).?The genes H19?PFKFB4?SFTPA1 low-expressed and hypermthylated in the longevity family individuals.Conclusions:? Longevity and ageing of humans are related to gene differential expression,and the longevity DEGs involve in cell immunity,ageing DEGs involve in humoral immunity.Gene expression profile is mildly correlated to longevity.?The specific ageing DEGs CCR6 and ID3 express negatively to age.?The specific longevity hyper-and hypo methylated genes are found,and the methylation profiles of some CpG sites in NFATC1 gene might correlate to the longevity in Guangxi Bama region.?H19,PFKFB4,SFTPA1 are both longevity-related low expressing genes and longevity-related hyper-methylated genes. |
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