Epigenetic clock and methylation studies in elephants

Natalia A. Prado, Janine L. Brown, Joseph A. Zoller, Amin Haghani, Mingjia Yao, Lora R. Bagryanova, Michael G. Campana, Jesús E. Maldonado, Ken Raj, Dennis Schmitt, Todd R. Robeck, Steve Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)
29 Downloads (Pure)


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.

Original languageEnglish
Article numbere13414
Number of pages11
JournalAging Cell
Issue number7
Early online date12 Jun 2021
Publication statusPublished - 15 Jul 2021

Bibliographical note

Funding Information: This work was mainly supported by the Paul G. Allen Frontiers Group (SH). Stipend and reagent support for NAP was provided through Dr. Janice Sanders and the George E. Burch Post-Doctoral Fellowship in Theoretical Medicine and Affiliated Theoretical Science. The Smithsonian Institution supported J.L.B, M.G.C., and J.E.M. The funders had no role in the study design, data collection, decision to publish, or preparation of the manuscript.

Open Access: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright: © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Citation: Prado, N. A., Brown, J. L., Zoller, J. A., Haghani, A., Yao, M., Bagryanova, L. R., Campana, M. G., Maldonado, J. E., Raj, K., Schmitt, D., Robeck, T. R., & Horvath, S. (2021). Epigenetic clock and methylation studies in elephants. Aging Cell, 20, e13414.

DOI: https://doi.org/10.1111/acel.13414


  • DNA methylation
  • aging
  • development
  • elephant
  • epigenetic clock


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