Abstract

Age‐associated DNA‐methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We present epigenetic clocks for Asian elephants (Elephas maximus), African elephants (Loxodonta africana), and both elephant species combined. Two additional human‐elephant clocks were constructed by combining human and elephant samples. Epigenome‐wide association studies identified elephant age‐related CpGs and their proximal genes. The products of these genes play important roles in cellular differentiation, organismal development, metabolism, and circadian rhythms. Intracellular events observed to change with age included the methylation of bivalent chromatin domains, and targets of polycomb repressive complexes. These readily available epigenetic clocks can be used for elephant conservation efforts where accurate estimates of age are needed to predict demographic trends.

Highlights

  • In comparison with many other mammals, elephants have remarkably long lives, with African (Loxodonta africana) and Asian (Elephas maximus) elephant lifespans exceeding 70 years and 80 years, respectively (Lahdenperä et al, 2014; Lee et al, 2012)

  • This study describes five epigenetic clocks for elephants, of which three are pure elephant clocks and two are multi-­species human/elephant clocks that are applicable to humans as well

  • The human-­elephant clocks for chronological and relative age demonstrate the feasibility of building epigenetic clocks for different species based on a single mathematical formula

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Summary

| INTRODUCTION

In comparison with many other mammals, elephants have remarkably long lives, with African (Loxodonta africana) and Asian (Elephas maximus) elephant lifespans exceeding 70 years and 80 years, respectively (Lahdenperä et al, 2014; Lee et al, 2012). The significance and specificity of these alterations remained a source of speculation until the development of an array-­based technology that permitted the quantification of methylation levels of specific CpG positions on the human genome With this advancement came the opportunity and insight to combine age-­related methylation changes of multiple DNA loci to develop a highly accurate age-­estimator (epigenetic clocks) for all human tissues (Field et al, 2018; Horvath & Raj, 2018). The hope of extending the benefits of these clocks to other animals was initially encouraged by the direct applicability of the human pan-­tissue clock on chimpanzee DNA methylation profiles This compatibility, could not be extended to other animals because of evolutionary genome sequence divergence (Horvath, 2013). We present several ready-­to-­use DNA methylation-­based age estimators (epigenetic clocks) for Asian and African elephants, the characteristics of age-­related CpGs that constitute the elephant epigenetic clocks, and how they compare with those of humans

| RESULTS
| DISCUSSION
Findings
| EXPERIMENTAL PROCEDURES
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