Exploring the ageing methylome in the model insect, Nasonia vitripennis

Abstract

Background: The ageing process is a multifaceted phenomenon marked by the gradual deterioration of cellular and organismal functions, accompanied by an elevated susceptibility to diseases. The intricate interplay between genetic and environmental factors complicates research, particularly in complex mammalian models. In this context, simple invertebrate organisms have been pivotal, but the current models lack detectable DNA methylation limiting the exploration of this critical epigenetic ageing mechanism. This study introduces Nasonia vitripennis, the jewel wasp, as an innovative invertebrate model for investigating the epigenetics of ageing. Leveraging its advantages as a model organism and possessing a functional DNA methylation system, Nasonia emerges as a valuable addition to ageing research.

Results: Whole-genome bisulfite sequencing unveiled dynamic alterations in DNA methylation, with differentially methylated CpGs between distinct time points in both male and female wasps. These changes were associated with numerous genes, enriching for functions related to telomere maintenance, histone methylation, and mRNA catabolic processes. Additionally, other CpGs were found to be variably methylated at each timepoint. Sex-specific effects on epigenetic entropy were observed, indicating differential patterns in the loss of epigenetic stability over time. Constructing an epigenetic clock containing 19 CpGs revealed a robust correlation between epigenetic age and chronological age.

Conclusions: Nasonia vitripennis emerges as a promising model for investigating the epigenetics of ageing, shedding light on the intricate dynamics of DNA methylation and their implications for age-related processes. This research not only expands the repertoire of ageing models but also opens avenues for deeper exploration of epigenetic mechanisms in the context of ageing.

Keywords: BS-seq; Entropy; Epigenetic clock; Epigenetics; Hymenoptera.

Fig. 1

Schematic overview of experimental design with study organism, Nasonia vitripennis. Image credit: M.E. Clark public domain

Fig. 2

a Kaplan-Meier survival curves for female (n = 70) and male (n = 67) Nasonia vitripennis adults. Shaded areas represent the 95% confidence intervals. b Estimated marginal means of methylation proportion per methylated CpG against chronological age. Shaded bars are 95% confidence intervals c Scatterplots of epigenetic entropy based on the 5290 age-related differentially methylated CpGs over time for male and female Nasonia. Each point is a single WGBS library made up of ten individuals. Lines represent the beta regression predictions d Scatterplot of epigenetic age versus chronological age of male (n=8) and female (n = 9) Nasonia samples. Each sample is made up of the whole bodies of ten individuals