Abstract
Aging is a universal process with profound consequences for health, disease, and survival. Across species, epigenetic modifications provide a molecular record of both time and exposure to the environment, making them powerful markers of biological aging. Some loci show patterns of epigenetic modification that are highly age-correlated; these methylation signals can be compiled to create epigenetic clocks capable of estimating chronological age with impressive precision.
Anguillid eels—long-lived, catadromous, semelparous fishes with environmentally-dependant growth and maturation—provide a unique opportunity to study aging in an animal with an unusual life history. By examining epigenetic aging in these eels, we may uncover conserved principles of aging that apply broadly across vertebrates, including humans.
The aim of the present study was to explore the effect of aging on global and CpG-specific methylation levels in the New Zealand short-finned eel (Anguilla australis), with the exploratory goal of creating an epigenetic clock predictive of chronological age derived from minimally-invasive samples. Skin and otolith samples were collected from fisheries offcuts, and chronological age was determined by counting annual growth rings in these otoliths. Whole-genome bisulphite sequencing was performed at ~15× coverage across individuals ranging from 7 to 23 years of age. Global and CpG-specific methylation levels were analysed in relation to age, and various regression models were tested for predictive capacity.
Significantly, gene ontology analysis of highly age-correlated loci revealed enrichment for pathways associated with canonical aging and disease processes, including Wnt/b-catenin and TGF-b signalling, immune regulation, and chondrocyte differentiation. These pathways are implicated in tissue homeostasis, immunosenescence, and osteoarthritis in humans, highlighting the deep conservation of molecular mechanisms underlying vertebrate aging.
This study presents the first comprehensive analysis of DNA methylation and age in Anguilla australis, identifying loci with methylation patterns enriched for conserved aging pathways. While the exploratory clock model developed here is not yet generalisable, the clear biological relevance of the methylation signal provides a foundation for future studies into epigenetic aging in anguillid eels. Establishing these principles in a divergent vertebrate model offers a powerful comparative framework for understanding the molecular basis of aging and age-related disease in humans, while also supporting conservation of this culturally significant taonga species.