Epigenetic clock and methylation studies in the rhesus macaque

Steve Horvath, Joseph A. Zoller, Amin Haghani, Anna J. Jasinska, Ken Raj, Charles E. Breeze, Jason Ernst, Kelli L. Vaughan, Julie A. Mattison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles underpinning them appear to be conserved at least across the mammalian class. This is exemplified by the successful development of epigenetic clocks for mice and several other mammalian species. Here, we describe epigenetic clocks for the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate in biological research. Using a custom methylation array (HorvathMammalMethylChip40), we profiled n = 281 tissue samples (blood, skin, adipose, kidney, liver, lung, muscle, and cerebral cortex). From these data, we generated five epigenetic clocks for macaques. These clocks differ with regard to applicability to different tissue types (pan-tissue, blood, skin), species (macaque only or both humans and macaques), and measure of age (chronological age versus relative age). Additionally, the age-based human-macaque clock exhibits a high age correlation (R = 0.89) with the vervet monkey (Chlorocebus sabaeus), another Old World species. Four CpGs within the KLF14 promoter were consistently altered with age in four tissues (adipose, blood, cerebral cortex, skin). Future studies will be needed to evaluate whether these epigenetic clocks predict age-related conditions in the rhesus macaque.

Original languageEnglish
Pages (from-to)2441-2453
Number of pages13
Issue number5
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
This study was supported by the Paul G. Allen Frontiers Group (PI SH). The rhesus macaque samples were contributed by the NIA NHP Core which is supported by the Intramural Research Program of the National Institute on Aging, NIH. Human tissue sample collection was supported by NIH funding through the NIMH and NINDS Institutes by the following grants: Manhattan HIV Brain Bank (MHBB): U24MH100931; Texas NeuroAIDS Research Center (TNRC): U24MH100930; National Neurological AIDS Bank (NNAB): U24MH100929; California NeuroAIDS Tissue Network (CNTN): U24MH100928; Data Coordinating Center (DCC): U24MH100925. Human blood samples were supported by 1U01AG060908-01 and R21MH107327. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the NNTC or NIH.

Publisher Copyright:
© 2021, The Author(s).


  • DNA methylation
  • Epigenetic clock
  • Nonhuman primate
  • Rhesus monkey


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