An epigenetic clock to estimate the age of living beluga whales

Abstract

DNA methylation data facilitate the development of accurate molecular estimators of chronological age or “epigenetic clocks.” We present a robust epigenetic clock for the beluga whale, Delphinapterus leucas, developed for an endangered population in Cook Inlet, Alaska, USA. We used a custom methylation array to measure methylation levels at 37,491 cytosine–guanine sites (CpGs) from skin samples of dead whales (n = 67) whose chronological ages were estimated based on tooth growth layer groups. Using these calibration data, a penalized regression model selected 23 CpGs, providing an R2 = 0.92 for the training data; and an R2 = 0.74 and median absolute age error = 2.9 years for the leave one out cross‐validation. We applied the epigenetic clock to an independent dataset of 38 skin samples collected with a biopsy dart from living whales between 2016 and 2018. Age estimates ranged from 11 to 27 years. We also report sex correlations in CpG data and describe an approach of identifying the sex of an animal using DNA methylation. The epigenetic estimators of age and sex presented here have broad applications for conservation and management of Cook Inlet beluga whales and potentially other cetaceans.

Multi-Tissue Methylation Clocks for Age and Sex Estimation in the Common Bottlenose Dolphin

“…Similar to previous work with other cetaceans, we found no evidence that accounting for sex was necessary for the development of the three BDAC clocks (Bors et al, 2020;Robeck et al, 2021b). Aging effects in males were highly correlated with those in females both in blood (R = 0.78) and skin (R = 0.62).…”

“…Recent efforts at developing less invasive methods with enhanced accuracy for age determination across multiple species, including marine mammals, has led to recent applications of species-specific DNA methylation (DNAm) profiles for the development of epigenetic aging clocks (Polanowski et al, 2014;Cole et al, 2017;Wang et al, 2017;Thompson et al, 2018;Beal et al, 2019;Bors et al, 2020;Prado et al, 2020b;Lu et al, 2021;Robeck et al, 2021b). DNAm is described as an epigenetic modification whereby a transfer of a methyl (CH 3 ) group from S-adenosyl methionine (SAM) to the fifth position of cytosine nucleotides, forming 5methylcytosine (5 mC) nucleotides (Smith and Meissner, 2013).…”

Accurate Epigenetic Aging in Bottlenose Dolphins (Tursiops truncatus), an Essential Step in the Conservation of at-Risk Dolphins

“…The present study stands out in its use of a longitudinal dataset from the U.S. Navy Marine Mammal Program (Navy). Since 1959, the Navy has expanded knowledge in bottlenose dolphin health and physiology [9,10]. The extensive tissue archive, paired with daily observational and medical records for individual dolphins, provides a unique opportunity for scientific research.…”

Development of epigenetic clocks for New Zealand livestock

“…As part of the model, a subset of features (CpG methylation sites) are selected which cumulatively give the best predictor for a set of outcomes (age). The two main parameters that are employed in the elastic net model are; (1) the mixing parameter (α) which controls the shrinkage type between ridge (α = 0) and LASSO regression (α = 1) and; (2) the penalty parameter (λ) which controls the stringency of penalty (higher values of λ lead to coefficients closer or equal to zero) 19 .…”

“…(2) the penalty parameter (λ) which controls the stringency of penalty (higher values of λ lead to coefficients closer or equal to zero) 19 .…”