Epigenetic age-predictor for mice based on three CpG sites

Han, Yang; Eipel, Monika; Franzen, Julia; Sakk, Vadim; Dethmers-Ausema, Bertien; Yndriago, Laura; Izeta, Ander; Haan, Gerald de; Geiger, Hartmut; Wagner, Wolfgang

doi:10.7554/elife.37462

Cited by 55 publications

(87 citation statements)

References 23 publications

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“…In addition, efforts are being invested in identifying clocks based on a handful of CpG sites since methylation arrays, RRBS, or WGBS remain relatively expensive compared to bisulfite pyrosequencing. In this aspect, Wolfgang Wagner's group has shown that measurements from just three CpG sites can accurately readout lifespan in both humans and mice (Weidner et al, 2014;Han et al, 2018). More recently, an epigenetic clock based on ribosomal DNA methylation was reported to be evolutionary conserved across several species (Wang and Lemos, 2019).…”

Section: Epigenetic-based Aging Clocksmentioning

confidence: 99%

DNA Methylation Biomarkers in Aging and Age-Related Diseases

2020

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Recent research efforts provided compelling evidence of genome-wide DNA methylation alterations in aging and age-related disease. It is currently well established that DNA methylation biomarkers can determine biological age of any tissue across the entire human lifespan, even during development. There is growing evidence suggesting epigenetic age acceleration to be strongly linked to common diseases or occurring in response to various environmental factors. DNA methylation based clocks are proposed as biomarkers of early disease risk as well as predictors of life expectancy and mortality. In this review, we will summarize key advances in epigenetic clocks and their potential application in precision health. We will also provide an overview of progresses in epigenetic biomarker discovery in Alzheimer's, type 2 diabetes, and cardiovascular disease. Furthermore, we will highlight the importance of prospective study designs to identify and confirm epigenetic biomarkers of disease.

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Section: Epigenetic-based Aging Clocksmentioning

confidence: 99%

DNA Methylation Biomarkers in Aging and Age-Related Diseases

2020

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“…Because the basic features of DNA methylation are conserved at least in closely related species or even taxa, the epigenetic clock based on the same informative CpGs identified in humans was found to also work reasonably well in chimpanzees (Pan troglodytes) (Horvath, 2013). Since then, species-specific epigenetic clocks have been constructed in chimpanzees (Ito, Udono, Hirata, & Inoue-Murayama, 2018), mice (Han et al, 2018), humpback whales (Megaptera novaeangliae) (Polanowski, Robbins, Chandler, & Jarman, 2014), Bechstein's bats (Myotis bechsteinii) (Wright et al, 2018), dogs and wolves (Janowitz Koch et al, 2016;Thompson, vonHoldt, Horvath, & Pellegrini, 2017) and in a long-lived seabird (Ardenna tenuirostris) (Paoli-Iseppi et al, 2019). Epigenetic clocks are characterized by very high accuracy when compared to more traditional methods of age estimation.…”

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A clockwork fish: Age prediction using DNA methylation‐based biomarkers in the European seabass

Anastasiadi

Piferrer

2019

Molecular Ecology Resources

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Age‐related changes in DNA methylation do occur. Taking advantage of this, mammalian and avian epigenetic clocks have been constructed to predict age. In fish, studies on age‐related DNA methylation changes are scarce and no epigenetic clocks have been constructed. However, in fisheries and population dynamics studies there is a need for accurate estimation of age, something that is often impossible for some economically important species with the currently available methods. Here, we used the European sea bass, a marine fish the age of which can be determined with accuracy, to construct a piscine epigenetic clock, the first one in a cold‐blooded vertebrate. We used targeted bisulfite sequencing to amplify 48 CpGs from four genes in muscle samples and applied penalized regressions to predict age. We thus developed an age predictor in fish that is highly accurate (0.824) and precise (2.149 years). In juvenile fish, accelerated growth due to elevated temperatures had no effect on age prediction, indicating that the clock is able to predict the chronological age independently of environmentally‐driven perturbations. An epigenetic clock developed using muscle samples accurately predicted age in samples of testis but not ovaries, possibly reflecting the reproductive biology of fish. In conclusion, we report the development of the first piscine epigenetic clock, paving the way for similar studies in other species. Piscine epigenetic clocks should be of great utility for fisheries management and conservation purposes, where age determination is of crucial importance.

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“…(for blood and buccal swabs, respectively). Alternative age prediction models were generated by machine learning as described before (Han et al 2018). In brief, we applied a penalized lasso and elastic net regression model from glmnet R package on the training set from BBA-seq data.…”

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confidence: 99%

New Targeted Approaches for Epigenetic Age Predictions

Han

Franzen

Stiehl

et al. 2019

Preprint

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Aging causes epigenetic modifications, which are utilized as a biomarker for the aging process.While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective highthroughput analysis. In this study, we utilized 4,650 Illumina BeadChip datasets of blood to select the best suited CpG sites for targeted analysis. DNA methylation analysis at these sites with either pyrosequencing or droplet digital PCR (ddPCR) revealed a high correlation with chronological age.In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower precision at individual CpGs. However, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often accompanied by a CTCF binding site at the peak. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified but reveals a stochastic pattern. Based on this, we have developed an alternative model for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Thus, the stochastic evolution of age-associated DNA methylation patterns, which seems to resemble epigenetic drift, enables epigenetic clocks for individual DNA strands.

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Epigenetic age-predictor for mice based on three CpG sites

Cited by 55 publications

References 23 publications

DNA Methylation Biomarkers in Aging and Age-Related Diseases

DNA Methylation Biomarkers in Aging and Age-Related Diseases

A clockwork fish: Age prediction using DNA methylation‐based biomarkers in the European seabass

New Targeted Approaches for Epigenetic Age Predictions

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