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

doi:10.1111/acel.13414

Epigenetic clock and methylation studies in elephants

Aging Cell. 2021 Jul;20(7):e13414. doi: 10.1111/acel.13414. Epub 2021 Jun 12.

Authors

Natalia A Prado^{1

2}, Janine L Brown¹, Joseph A Zoller³, Amin Haghani⁴, Mingjia Yao³, Lora R Bagryanova⁵, Michael G Campana², Jesús E Maldonado², Ken Raj⁶, Dennis Schmitt⁷, Todd R Robeck⁸, Steve Horvath^{3

4}

Affiliations

¹ Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, VA, USA.
² Center for Conservation Genomics, Smithsonian Conservation Biology Institute, Washington, DC, USA.
³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
⁴ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁵ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot, UK.
⁷ College of Agriculture, Missouri State University, Springfield, MO, USA.
⁸ SeaWorld Parks and Entertainment, Orlando, FL, USA.

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.

Keywords: DNA methylation; aging; development; elephant; epigenetic clock.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics*
Animals
Elephants
Epigenomics / methods*
Methylation