Epigenetic clock and methylation studies in vervet monkeys

Anna J Jasinska; Amin Haghani; Joseph A Zoller; Caesar Z Li; Adriana Arneson; Jason Ernst; Kylie Kavanagh; Matthew J Jorgensen; Julie A Mattison; Kevin Wojta; Oi-Wa Choi; Joseph DeYoung; Xinmin Li; Andrew W Rao; Giovanni Coppola; Nelson B Freimer; Roger P Woods; Steve Horvath

doi:10.1007/s11357-021-00466-3

Epigenetic clock and methylation studies in vervet monkeys

Geroscience. 2022 Apr;44(2):699-717. doi: 10.1007/s11357-021-00466-3. Epub 2021 Sep 30.

Authors

Anna J Jasinska^{1

2

3}, Amin Haghani⁴, Joseph A Zoller⁵, Caesar Z Li⁵, Adriana Arneson^{6

7}, Jason Ernst^{6

7}, Kylie Kavanagh^{8

9}, Matthew J Jorgensen⁸, Julie A Mattison¹⁰, Kevin Wojta^{11

12}, Oi-Wa Choi¹¹, Joseph DeYoung¹¹, Xinmin Li¹³, Andrew W Rao¹³, Giovanni Coppola^{11

12}, Nelson B Freimer^{11

4}, Roger P Woods^{11

12}, Steve Horvath^{14

15}

Affiliations

¹ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. ankajasinska@gmail.com.
² Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. ankajasinska@gmail.com.
³ Eye On Primates, Los Angeles, CA, USA. ankajasinska@gmail.com.
⁴ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Interdepartmental Bioinformatics Program, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁷ Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁸ Department of Pathology, Section On Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, 27157-1040, USA.
⁹ Department of Biomedical Sciences, University of Tasmania, Hobart, Australia.
¹⁰ Translational Gerontology Branch, National Institute On Aging Intramural Research Program, National Institute of Health, Gaithersburg, USA.
¹¹ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, USA.
¹³ Technology Center for Genomics & Bioinformatics, Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
¹⁴ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
¹⁵ Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.

Abstract

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.

Keywords: Aging; DNA methylation; Development; Epigenetic clock; Monkey; Vervet.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Animals
Chlorocebus aethiops
DNA Methylation
Epigenesis, Genetic*
Epigenomics*
Longevity
Macaca mulatta / genetics
Mammals

Abstract

Publication types

MeSH terms

Grants and funding