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.
Highlights
Non-human primates (NHPs) are regarded as critical animal models used in biomedical research [1,2,3,4,5,6] and key reference species used for constructing a comparative framework essential for evolutionary biology studies [7, 8]
Specialized tools are needed for the assessment of aging processes in NHP models in the context of the environmental and genetic factors regulating natural aging, the pathogenesis of age-related conditions, and the development and testing of anti-aging therapies
All animals used in this study were Caribbean-origin vervet monkeys (Chlorocebus sabaeus) from the Vervet Research Colony (VRC) at Wake Forest School of Medicine
Summary
Non-human primates (NHPs) are regarded as critical animal models used in biomedical research [1,2,3,4,5,6] and key reference species used for constructing a comparative framework essential for evolutionary biology studies [7, 8]. NHPs are invaluable models for studying the pathomechanisms of age-related diseases, developing novel anti-aging treatments, GeroScience and performing preclinical testing of such therapies before translation to human subjects [12]. Specialized tools are needed for the assessment of aging processes in NHP models in the context of the environmental and genetic factors regulating natural aging, the pathogenesis of age-related conditions, and the development and testing of anti-aging therapies. Whereas physiological conditions (e.g., BMI and menopause), pathologies (e.g., cancers and neurodegenerative diseases), and environmental factors (e.g., diet, exercise, and HIV infection) can affect the trajectory of DNAm age [15, 19,20,21,22,23], the pace of DNAm age is a heritable genetic trait linked to several genomic regions [24,25,26]
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