The epigenetic and regulatory hallmarks of ageing and the role of germline-soma interaction

de Coriolis, Jean-Charles William Marie Gabriel (2026) The epigenetic and regulatory hallmarks of ageing and the role of germline-soma interaction. Doctoral thesis, University of East Anglia.

Preview

PDF Download (19MB) | Preview

Abstract

This thesis investigates how germline–soma communication shapes molecular ageing in a vertebrate system, using zebrafish to integrate transcriptomic analysis, DNA methylation–based ageing biomarkers, and pharmacological intervention. The overarching aim is to determine how reproductive status influences somatic regulatory programmes and epigenetic ageing trajectories across tissues and lifespan. Chapter 2 demonstrates that germline removal induces a consistent reorganisation of somatic gene expression. Germline-free fish upregulate DNA repair, cell-cycle control, and genome maintenance pathways across multiple tissues, whereas germline-carrying fish prioritise metabolic and growth-associated processes. Following genotoxic stress, germline-free fish activate somatic repair responses more rapidly, while testes in germline-carrying fish show the strongest repair response overall, indicating tissue-specific allocation of maintenance investment. Chapter 3 develops and benchmarks over 3,000 cross-sectional epigenetic clock models, demonstrating that clock accuracy depends strongly on tissue context and modelling strategy. Chapter 4 applies optimised cross-sectional clocks across multiple tissues and identifies a robust subset of CpG sites with shared age-associated trajectories alongside extensive tissue-specific methylation patterns, indicating that epigenetic ageing comprises both conserved and tissue-restricted components. Chapter 5 adopts a longitudinal framework to track within-individual epigenetic ageing over time. Germline-free fish are epigenetically younger early in life but exhibit steeper late-life trajectories. These shifts are associated with age- and germline-dependent hypomethylation at robustly selected CpG sites and occur alongside preserved locomotor function in old age. Chapter 6 examines rapamycin effects across two experimental designs. Short-term late-life exposure reveals sex-specific epigenetic age acceleration accompanied by reduced male fertility and altered behaviour. Lifelong exposure identifies increased ovarian pathology in genome-unstable fish alongside reduced anxiety-like behaviour in wild-type animals. Collectively, these findings establish germline status as a key regulator of somatic epigenetic ageing dynamics, highlight fundamental differences between cross-sectional and longitudinal ageing measures. This demonstrates that interventions targeting nutrient-sensing pathways have context-dependent and genotype-specific effects.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	31 Mar 2026 14:18
Last Modified:	31 Mar 2026 14:18
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102675
DOI:

Downloads

Actions (login required)

View Item