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Targeted methods for epigenetic age predictions in mice

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...

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Autores principales: Han, Yang, Nikolić, Miloš, Gobs, Michael, Franzen, Julia, de Haan, Gerald, Geiger, Hartmut, Wagner, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775437/
https://www.ncbi.nlm.nih.gov/pubmed/33384442
http://dx.doi.org/10.1038/s41598-020-79509-2
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author Han, Yang
Nikolić, Miloš
Gobs, Michael
Franzen, Julia
de Haan, Gerald
Geiger, Hartmut
Wagner, Wolfgang
author_facet Han, Yang
Nikolić, Miloš
Gobs, Michael
Franzen, Julia
de Haan, Gerald
Geiger, Hartmut
Wagner, Wolfgang
author_sort Han, Yang
collection PubMed
description 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.
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spelling pubmed-77754372021-01-07 Targeted methods for epigenetic age predictions in mice Han, Yang Nikolić, Miloš Gobs, Michael Franzen, Julia de Haan, Gerald Geiger, Hartmut Wagner, Wolfgang Sci Rep Article 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. Nature Publishing Group UK 2020-12-31 /pmc/articles/PMC7775437/ /pubmed/33384442 http://dx.doi.org/10.1038/s41598-020-79509-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Han, Yang
Nikolić, Miloš
Gobs, Michael
Franzen, Julia
de Haan, Gerald
Geiger, Hartmut
Wagner, Wolfgang
Targeted methods for epigenetic age predictions in mice
title Targeted methods for epigenetic age predictions in mice
title_full Targeted methods for epigenetic age predictions in mice
title_fullStr Targeted methods for epigenetic age predictions in mice
title_full_unstemmed Targeted methods for epigenetic age predictions in mice
title_short Targeted methods for epigenetic age predictions in mice
title_sort targeted methods for epigenetic age predictions in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775437/
https://www.ncbi.nlm.nih.gov/pubmed/33384442
http://dx.doi.org/10.1038/s41598-020-79509-2
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