Genome Wide Analysis of Epigenetic Changes in Aging

• Applicants: Professor Dr. Ivan Gesteira Costa Filho; Professor Dr. Alexander Meissner; Professor Dr. Wolfgang Wagner
• Subject Area: General Genetics and Functional Genome Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458369830

Human aging is linked to characteristic DNA methylation changes, which have been mostly investigated with Illumina BeadChip datasets. The heterogeneity of epigenetic aging within a sample is hence missed and the association with chromatin accessibility or the histone code remains also largely unclear. Here, we aim for an urgently needed Reference Epigenome of Aging based on whole genome bisulfite sequencing data (WGBS) in combination with open chromatin sequencing (ATAC-seq) for 120 peripheral blood samples (0 to 80 years). This will facilitate a range of studies including the investigation of neighboring CpGs to explore the underlying age-related mechanism. It will also enable to estimate the heterogeneity in cellular aging, which will be complemented with barcoded bisulfite amplicon sequencing (BBA-seq). Furthermore, samples of 5 young (18-25 years) and 5 elderly donors (70-80 years) will be analyzed with single cell ATAC-seq, and single cell RNA-seq (both 10x genomics), to gain additional insight into regulatory interplay. To maximize insights from the matched samples, ChIP-seq of histone modifications (H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3) and methyl-ATAC-seq will also be analyzed for 5 young and 5 elderly donors to also incorporate the interaction of histones and open chromatin with the methylome. The complementary expertise of the PIs will allow an unprecedented integration of multiple regulatory layers to immediately serve as a much needed reference and already inform on functional interaction as well as the heterogeneity of epigenetic aging within a given sample.

• DFG Programme: Research Grants