Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

Horvath, Steve; Haghani, Amin; Zoller, Joseph A.; Raj, Ken; Sinha, Indranil; Robeck, Todd R.; Black, Pete; Couzens, Aidan M. C.; Lau, Clive L.F.; Manoyan, Meghety; Ruiz, Y. Aviles; Talbott, Annais; Belov, Katherine; Hogg, Carolyn J.; Sears, Karen E.

doi:10.1007/s11357-022-00569-5

Cited by 14 publications

(10 citation statements)

References 78 publications

(71 reference statements)

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“…Recently published epigenetic clocks for equids (Horvath, Haghani, et al, 2022; Horvath, Haghani, Zoller, et al, 2022; Larison et al, 2021), marsupials (Horvath, Haghani, et al, 2022; Horvath, Haghani, Zoller, et al, 2022), or odontocetes (Robeck, Fei, Lu, et al, 2021) have leveraged the same mammalian methylation array to support development of epigenetic clocks for targeted taxa. Epigenetic clocks targeting multiple species provide additional flexibility by leveraging data from related species that are better represented by available sample numbers from known age individuals.…”

Section: Discussionmentioning

confidence: 99%

“…The first DNA methylation‐based age predictors, referred to as “epigenetic clocks”, were developed for human saliva (Bocklandt et al, 2011) and later for all tissues (Horvath, 2013). Subsequent studies described epigenetic clocks for mice (Petkovich et al, 2017; Stubbs et al, 2017; Thompson et al, 2018; Wang et al, 2017) and many other mammalian species including bats (Wilkinson et al, 2021), primates (Horvath, Zoller, Haghani, Jasinska, et al, 2021; Horvath, Zoller, Haghani, Lu, et al, 2021; Jasinska et al, 2021), equids (Horvath, Haghani, et al, 2022; Horvath, Haghani, Zoller, et al, 2022; Larison et al, 2021), deer (Lemaître et al, 2022), dogs (Horvath, Lu, et al, 2022), cats (Raj et al, 2021), bottlenose dolphins (Beal et al, 2019; Robeck, Fei, Lu, et al, 2021), beluga whales (Bors et al, 2020). Methylation levels at highly conserved cytosines allows one to define pan mammalian ageing clocks that apply to all mammalian species (Lu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation‐based biomarkers for ageing long‐lived cetaceans

Parsons

Haghani²,

Zoller

et al. 2023

Molecular Ecology Resources

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Epigenetic approaches for estimating the age of living organisms are revolutionizing studies of long‐lived species. Molecular biomarkers that allow age estimates from small tissue biopsies promise to enhance studies of long‐lived whales, addressing a fundamental and challenging parameter in wildlife management. DNA methylation (DNAm) can affect gene expression, and strong correlations between DNAm patterns and age have been documented in humans and nonhuman vertebrates and used to construct “epigenetic clocks”. We present several epigenetic clocks for skin samples from two of the longest‐lived cetaceans, killer whales and bowhead whales. Applying the mammalian methylation array to genomic DNA from skin samples we validate four different clocks with median errors of 2.3–3.7 years. These epigenetic clocks demonstrate the validity of using cytosine methylation data to estimate the age of long‐lived cetaceans and have broad applications supporting the conservation and management of long‐lived cetaceans using genomic DNA from remote tissue biopsies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA methylation‐based biomarkers for ageing long‐lived cetaceans

Parsons

Haghani²,

Zoller

et al. 2023

Molecular Ecology Resources

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“…Excitingly, the RheMacAge clock comes online at a time when resources for studying epigenetic aging in nonhuman mammals are expanding more generally. For example, the HorvathMammalMethylChip has already been deployed to study the effects of hibernation on epigenetic aging in yellow-bellied marmots (Pinho et al, 2022), to examine postnatal development of the epigenome in opossums and other marsupials (Horvath et al, 2022), and to evaluate the potential lifespan-extending effects of partial cell reprogramming in a mouse model of premature aging (Browder et al, 2022). Our RheMacAge model, which takes a sliding-window approach, provides a useful alternative to the HorvathMammalMethylChip for researchers who wish to look at how DNA methylation varies across the genome more broadly, by coupling applications of the clock with differential or allele-specific methylation analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, this limitation also applies to recently developed multi-species arrays like the HorvathMammalMethylChip (Arneson et al, 2021). The multi-species array has provided extensive insight into epigenetic aging across many mammals (e.g., Horvath et al 2022; Wilkinson et al 2021) while capturing DNA methylation at only 38,000 highly conserved, non-randomly distributed CpG sites. Consequently, generalizable tools to study epigenetic aging using BS-seq data are also needed.…”

Section: Introductionmentioning

confidence: 99%

A generalizable epigenetic clock captures aging in two nonhuman primates

Goldman¹,

Watowich

Chiou

et al. 2022

Preprint

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Epigenetic clocks generated from DNA methylation array data provide important insights into biological aging, disease susceptibility, and mortality risk. However, these clocks cannot be applied to high-throughput, sequence-based datasets more commonly used to study nonhuman animals. Here, we built a generalizable epigenetic clock using genome-wide DNA methylation data from 493 free-ranging rhesus macaques. Using a sliding-window approach that maximizes generalizability across datasets and species, this model predicted age with high accuracy (+/- 1.42 years) in held-out test samples, as well as in two independent test sets: rhesus macaques from a captive population (n=43) and wild baboons in Kenya (n=271). Our model can also be used to generate insight into the factors hypothesized to alter epigenetic aging, including social status and exposure to traumatic events. Our results thus provide a flexible tool for predicting age in other populations and species and illustrate how connecting behavioral data with the epigenetic clock can uncover social influences on biological age.

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“…(i.5) Marsupials (infraorder Marsupialia). The first study to assay methylation in relation to age in marsupials (Horvath et al, 2022d) was conducted in gray short-tailed opossum [Monodelphis domestica (Wagner)], a South American species with a pseudo-pouch, similar to those of male thylacines [Thylacinus cynocephalus (Harris)]. This study used a universal mammal array to develop a clock able to predict age with a MEP of 3-4 months.…”

Section: Speciesmentioning

confidence: 99%

Biological clocks as age estimation markers in animals: a systematic review and meta‐analysis

et al. 2023

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Various biological attributes associated with individual fitness in animals change predictably over the lifespan of an organism. Therefore, the study of animal ecology and the work of conservationists frequently relies upon the ability to assign animals to functionally relevant age classes to model population fitness. Several approaches have been applied to determining individual age and, while these methods have proved useful, they are not without limitations and often lack standardisation or are only applicable to specific species. For these reasons, scientists have explored the potential use of biological clocks towards creating a universal age‐determination method. Two biological clocks, tooth layer annulation and otolith layering have found universal appeal. Both methods are highly invasive and most appropriate for post‐mortem age‐at‐death estimation. More recently, attributes of cellular ageing previously explored in humans have been adapted to studying ageing in animals for the use of less‐invasive molecular methods for determining age. Here, we review two such methods, assessment of methylation and telomere length, describing (i) what they are, (ii) how they change with age, and providing (iii) a summary and meta‐analysis of studies that have explored their utility in animal age determination. We found that both attributes have been studied across multiple vertebrate classes, however, telomere studies were used before methylation studies and telomere length has been modelled in nearly twice as many studies. Telomere length studies included in the review often related changes to stress responses and illustrated that telomere length is sensitive to environmental and social stressors and, in the absence of repair mechanisms such as telomerase or alternative lengthening modes, lacks the ability to recover. Methylation studies, however, while also detecting sensitivity to stressors and toxins, illustrated the ability to recover from such stresses after a period of accelerated ageing, likely due to constitutive expression or reactivation of repair enzymes such as DNA methyl transferases. We also found that both studied attributes have parentally heritable features, but the mode of inheritance differs among taxa and may relate to heterogamy. Our meta‐analysis included more than 40 species in common for methylation and telomere length, although both analyses included at least 60 age‐estimation models. We found that methylation outperforms telomere length in terms of predictive power evidenced from effect sizes (more than double that observed for telomeres) and smaller prediction intervals. Both methods produced age correlation models using similar sample sizes and were able to classify individuals into young, middle, or old age classes with high accuracy. Our review and meta‐analysis illustrate that both methods are well suited to studying age in animals and do not suffer significantly from variation due to differences in the lifespan of the species, genome size, karyotype, or tissue type but rather that quantitative method, patterns of inheritance, and environmental factors should be the main considerations. Thus, provided that complex factors affecting the measured trait can be accounted for, both methylation and telomere length are promising targets to develop as biomarkers for age determination in animals.

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Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

Cited by 14 publications

References 78 publications

DNA methylation‐based biomarkers for ageing long‐lived cetaceans

DNA methylation‐based biomarkers for ageing long‐lived cetaceans

A generalizable epigenetic clock captures aging in two nonhuman primates

Biological clocks as age estimation markers in animals: a systematic review and meta‐analysis

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