Targeted methods for epigenetic age predictions in mice
Scientific Reports, vol. 10, pp. 22439
Abstract
Age-associated DNA methylation reflects aspect of biological aging-therefore epigenetic clocks for mice can elucidate how the aging process in this model organism is affected by specific treatments or genetic background. Initially, age-predictors for mice were trained for genome-wide DNA methylation profiles and we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three age-associated genomic regions. Here, we established alternative approaches using droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CG dinucleotides (CpGs) the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified at murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the single-read age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe alternative targeted methods for epigenetic age predictions that provide new perspectives for aging-intervention studies in mice.
Authors 7
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany
Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany
Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany
Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany
Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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University Medical Center Groningen
Affiliation as printed
Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, the Netherlands
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Affiliation as printed
Institute of Molecular Medicine, Ulm University, 89081, Ulm, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany. wwagner@ukaachen.de
Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany. wwagner@ukaachen.de
Institute for Biomedical Engineering – Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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