Epigenetic clock and methylation studies in vervet monkeys

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, 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 hypermethylated 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 age estimation of wild-born animals and anti-aging studies in vervets.

Pan-primate DNA methylation clocks

“…Following tracheal intubation, isoflurane (2%, 2L/min, by inhalation) was used to maintain a surgical plane of anesthesia throughout surgery. Cesarean section was performed at gestational day 165 (0.9 of gestation) using standard sterile techniques as previously described 30,50 . Following hysterotomy, the umbilical cord was identified and used for fetal exsanguination with both maternal and fetal baboon under general anesthesia as approved by the American Veterinary Medical Association Panel on Euthanasia 51 .…”

“…The data from other monkeys are described in the companion papers for rhesus macaque (n=283 samples from skin, blood, adipose, cerebral cortex, liver, lung, muscle 31 ), vervet monkey (n=240 samples from whole blood, prefrontal cortex and liver 30 ), and common marmosets (n=95 blood samples 32 ).…”

“…In addition, these biomarkers can also be used to evaluate the effect of agerelated conditions and various stress factors on the aging trajectory 19,29 26 21-25 . In previous publications, we have presented epigenetic clocks for vervet monkey 30 , rhesus macaque 31 , common marmosets 32 . Here we present epigenetic clocks for baboons and all five primate species.…”

Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus)

“…Gait speed was significantly associated with cognitive performance at one year in both the WFMT and the DR task. This period of time translates to roughly a three-to-four year follow up in humans, based on the maximum lifespans of vervets (~30 years [49]) and humans (~122 years [50]). The association between slow gait and later cognitive impairment aligns well with longitudinal clinical surveys showing similar temporal dynamics between physical and cognitive impairment (e.g., [15, 16, 20, 17–19]).…”

DNA methylation age analysis of rapamycin in common marmosets

“…To validate the vervet clock cross species, we utilized n=240 methylation arrays profiling blood, prefrontal brain cortex and liver from the vervet monkey described in a companion paper 24 . The methylation data were generated on the same array platform (MammalMethylChip40).…”