Establishing a tractable epigenetic clock in the parasitoid jewel wasp Nasonia vitripennis

Ageing is a complex biological process characterised by the progressive decline of physiological integrity, leading to impaired function and increased mortality. It is the primary risk factor for many diseases, motivating extensive research into its underlying mechanisms. Ageing is shaped by intricate interactions between genetic and environmental factors, complicating studies in complex mammalian models. Consequently, much research relies on invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. These models lack detectable DNA methylation, limiting their utility for investigating epigenetic alterations, a primary hallmark of ageing. Epigenetic clocks, based on DNA methylation, serve as robust biomarkers of biological age, but the mechanisms that regulate these clocks and their functional significance remain unclear. Progress has been constrained by the absence of short-lived, genetically tractable organisms with functional DNA methylation. The jewel wasp, Nasonia vitripennis, offers a unique opportunity, combining a functional DNA methylation system with a short lifespan and well-established experimental tools. Although an epigenetic clock(definition) exists in Nasonia, its sensitivity to environmentally driven, plastic ageing processes has yet to be explored. This thesis aims to develop a tractable epigenetic clock in N. vitripennis, creating a novel insect model to study epigenetic ageing. Through lifespan experiments, next-generation sequencing, and bioinformatic analyses, I assess how anti-ageing interventions including diapause, calorie restriction, and α-ketoglutarate supplementation modulate the epigenetic clock. These studies explore both the biology of epigenetic clocks and the extent to which they can be modulated by environmental and pharmacological factors. By establishing a malleable insect epigenetic clock, this work will open a new avenue in biogerontology. It provides a platform to investigate the molecular mechanisms driving clock plasticity and offers insights into interventions thatmay delay or reverse age-related decline. This model has the potential to advance our understanding of the biology of ageing and inform strategies to improve healthspan(definition) and longevity.