Searching for shared epigenetic clocks: evaluating ultra-conserved markers in a de novo genome assembly of the albacore tuna

Accurate age estimation is key to understanding life history, population ecology, and effective management of valuable commercial and ecologically relevant species. While DNA methylation-based epigenetic clocks are well developed in mammals, their application in fish is limited. In contrast to mammals, fish lack identified universal fish epigenetic markers. Here we explore the potential of ultra-conserved elements (UCEs) as age predictor markers in albacore tuna (Thunnus alalunga), a worldwide distributed and commercially valuable teleost fish. We produced a de novo reference genome of the albacore tuna in order to facilitate accurate mapping of bisulfite sequencing reads and identify conserved genomic regions. From muscle tissue samples spanning an age range of 0.03 to 17.69 years, we profiled methylation at UCEs and identified loci whose methylation levels were strongly correlated with age. By selecting an optimized subset of these regions, we constructed an epigenetic clock that predicts age with a median absolute error of 0.88 years. This demonstrates that UCEs represent a conserved set of age markers in teleosts and supports their potential for constructing shared epigenetic clocks between teleost species. To complement the clock construction, we conducted the first epigenome-wide association study (EWAS) of age in a fish species, enabling a broader characterization of age-associated methylation patterns beyond the CpGs included in the predictive model. This epigenetic aging strategy offers a non-lethal, field-applicable solution to age estimation from small tissue biopsies, avoiding otolith sampling and reducing the resources required to develop species-specific clocks.