Deciphering the link of DNA methylation with aging through population multi-omics analysis

Author(s):
Liu, Y.
Published
2026
Publication type
Doctoral Thesis

Abstract

The vision of aging research is to allow people to live healthier for longer. A promising path toward this goal is identifying epigenetic changes that accumulate across the lifespan, as they are considered one of the five primary hallmarks driving the aging process. By taking DNA methylation as an entry point, this thesis aims to investigate how aging affects methylation at functionally relevant genomic loci and how these methylation patterns are regulated, thereby advancing our mechanistic understanding of the aging process and age-related diseases. To achieve this, a range of omics data in a large collection of individuals from the population-based cohort was analyzed. Chapter 2 investigates the epigenetic regulation of cPCDH genes in humans using genome-wide methylation quantitative trait locus (meQTL) analysis. Chapter 3 explores the impact of age on X‑chromosome methylation in females. Finally, Chapter 4 focuses on developing a novel, interpretable aging biomarker using age‑related variably methylated CpGs (aVMCs).

AgingDNA methylationAge-related variably methylated CpGs (aVMCs)Methylation quantitative trait locus (meQTL) analysisX chromosomeWomenEpigenetic clocksVarianceEntropyGene expression
Defense date
2026-06-11
Language
English
Supervisor(s)
Heijmans, B.T.
Advisor(s)
Clemens-Daxinger, L.
Committee member(s)
Mooijaart, S.P.; Peters, D.J.M.; Marks, H.; Dongen, J. van
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/4304974
doi
10.60602/1887-4304974
ISBN(s)
9789465344263