DNA methylation age analysis of rapamycin in common marmosets

Abstract

Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

Epigenetic age prediction

“…Since the advent of DNAm age prediction for humans, age predictors have been created for other species; mice (Table 4 ), rats (Horvath, Singh, et al, 2020 ; Levine et al, 2020 ), dogs (Thompson et al, 2017 ; Wang et al, 2020 ), wolves (Thompson et al, 2017 ), humpback whales (Polanowski et al, 2014 ), chimpanzees (Guevara et al, 2020 ; Ito et al, 2018 ), marmosets (Horvath, Zoller, Haghani, Lu, et al, 2020 ), naked mole rats (Lowe et al, 2020 ), sea bass (Anastasiadi & Piferrer, 2020 ) and zebrafish (Mayne et al, 2020 ) (see Table 5 for a list of non‐human/mouse epigenetic clocks). In 2017, three mouse epigenetic clocks were developed primarily using reduced representation bisulphite sequencing (RRBS) data.…”

Pan-primate DNA methylation clocks

“…We excluded the common marmoset from our DNA methylation study of sex differences in primates, because marmosets appear to have a unique characteristic when it comes to DNA methylation studies in mammals: it is not possible to predict sex on the basis of methylation data in common marmosets 32 . We used the data from the remaining four primates to identify sex related CpGs in multiple tissues.…”

“…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.…”

Epigenetic clock and methylation studies in gray short-tailed opossums

“…DNA methylation-based age estimators have been developed for many mammalian species but not yet for opossums [32][33][34][35][36][37][38][39][40]. Here, we present highly accurate epigenetic clocks that apply to both humans and opossum.…”