The effect of age on human monocyte epigenetics and function

Abstract

As an individual ages their immune system undergoes a series of cellular, transcriptional and epigenomic changes. Using RRBS and RNA-Sequencing data collected from a group of 46 healthy participants across an age range, bioinformatics techniques were used to characterise the effect of age on the epigenome and transcriptome of immune cells. This project looks specifically at a single cell type; monocytes rather than a tissue, such as blood, to characterise cell specific changes. Methylation changes were observed to be tissue and cell specific, so analysing them in a single cell type can better elucidate the mechanism by which it undergoes ageing and thus how these changes affect the heterogeneous cell population from which it is extracted in vivo. Spearman correlation analysis, differential expression analysis and functional enrichment analysis were used to identify which genes and pathways exhibit changes with age, be it in their methylation level or their transcription. It was determined that differentially methylated regions often mapped to genes involved in phosphorylation, signal transduction, DNA binding and cellular projections. Furthermore, differentially expressed regions mapped to genes involved in immune functions, specifically response to bacterial lipoprotein and lipopeptide. The study attempted to filter the large RRBS experimental dataset using CpGs identified by Horvath (2013), to reduce the dataset and enrich it for age-associated regions. This only revealed one region, possibly due to the differences in distribution of the dataset. In conclusion, many of the terms found to be enriched in both methylation and transcription analysis were previously reported to change with age.