Larval diapause slows adult epigenetic aging in an insect model, <i>Nasonia vitripennis</i>.

Abstract

Epigenetic clocks based on DNA methylation provide robust biomarkers of biological age, yet the mechanistic basis and functional significance of slowing these clocks remain unclear. Progress has been limited by the lack of short-lived, genetically tractable model organisms with functional DNA methylation systems. The jewel wasp, <i>Nasonia vitripennis</i>, offers a unique solution. It combines a functional DNA methylation system with a short lifespan and established tools for experimental manipulation. We previously developed an epigenetic clock in <i>Nasonia</i>, but whether this clock reflects plastic, environmentally driven aging processes was unknown. Here, we test this directly by experimentally inducing larval diapause, a naturally occurring developmental arrest triggered by environmental cues. Diapause extended median adult lifespan by 36% and significantly slowed the rate of epigenetic aging. Using whole-genome bisulfite sequencing across multiple adult timepoints, we show that while adults that have passed through diapause as larvae initially emerge epigenetically older, their subsequent epigenetic aging proceeds 29% more slowly than adults that have not passed through diapause as larvae. Clock CpGs were enriched for gene ontology terms related to conserved nutrient-sensing and developmental pathways, including insulin/IGF signaling and mTOR, supporting the established mechanistic link between development and epigenetic aging. These findings demonstrate that epigenetic aging is plastic in <i>Nasonia</i> and can be experimentally modulated by early-life environment, establishing this animal model as a tractable system for dissecting the causal mechanisms of epigenetic aging.