An epigenetic clock to estimate the age of living beluga whales

Abstract

IntroductionDNA 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.Methods and ResultsWe 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 data set 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.DiscussionThe 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 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[1, 23]. 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 a surge in the application of species-specific DNA methylation profiles for the development of epigenetic aging clocks[1, 3, 17–23]. DNA methylation (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 5-methylcytosine (5mC) nucleotides[24].…”

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

“…The final model retained 112 CpG sites for the blood clock and 195 CpG for the multitissue clock (Figure 1, Figure S1-S2). R2 values for the LOIOCV predictions were 0.97 and 0.95 for the blood and multi-tissue clocks, respectively, compared to R2 = 0.74 previously reported for both dolphin and beluga clocks [6,10]. The final epigenetic clocks were highly accurate, with a median absolute LOIOCV prediction error of 2.0 years for the blood clock and 2.5 years for the multi-tissue clock.…”

“…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.…”

Age group DNA methylation differences in lemon sharks (Negaprion brevirostris): Implications for future age estimation tools

“…Over the last decade, several epigenetic clocks using DNA methylation to estimate chronological (actual or real age) and biological age (physiological age, how old an individual seems) have been successfully developed across diverse taxa (Beal et al, 2019 ; Bors et al, 2021 ; Chen et al, 2016 ; De Paoli‐Iseppi et al, 2019 ; Horvath & Raj, 2018 ; Polanowski et al, 2014 ; Salameh et al, 2020 ). Chronological epigenetic clocks specifically correlate percent DNA methylation at CpG sites (a Cytosine followed by a Guanine in the same DNA strand) to age through multiple regression analyses producing highly accurate estimations (correlation coefficient, r 2 , ranging from 0.70 to 0.99).…”