Targeted methods for epigenetic age predictions in mice

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 me...

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Autores principales:	Yang Han, Miloš Nikolić, Michael Gobs, Julia Franzen, Gerald de Haan, Hartmut Geiger, Wolfgang Wagner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3775f630f6454da794ff215f2b0461c3
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spelling	oai:doaj.org-article:3775f630f6454da794ff215f2b0461c32021-12-02T13:46:47ZTargeted methods for epigenetic age predictions in mice10.1038/s41598-020-79509-22045-2322https://doaj.org/article/3775f630f6454da794ff215f2b0461c32020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79509-2https://doaj.org/toc/2045-2322Abstract 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.Yang HanMiloš NikolićMichael GobsJulia FranzenGerald de HaanHartmut GeigerWolfgang WagnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yang Han Miloš Nikolić Michael Gobs Julia Franzen Gerald de Haan Hartmut Geiger Wolfgang Wagner Targeted methods for epigenetic age predictions in mice
description	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.
format	article
author	Yang Han Miloš Nikolić Michael Gobs Julia Franzen Gerald de Haan Hartmut Geiger Wolfgang Wagner
author_facet	Yang Han Miloš Nikolić Michael Gobs Julia Franzen Gerald de Haan Hartmut Geiger Wolfgang Wagner
author_sort	Yang Han
title	Targeted methods for epigenetic age predictions in mice
title_short	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_sort	targeted methods for epigenetic age predictions in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3775f630f6454da794ff215f2b0461c3
work_keys_str_mv	AT yanghan targetedmethodsforepigeneticagepredictionsinmice AT milosnikolic targetedmethodsforepigeneticagepredictionsinmice AT michaelgobs targetedmethodsforepigeneticagepredictionsinmice AT juliafranzen targetedmethodsforepigeneticagepredictionsinmice AT geralddehaan targetedmethodsforepigeneticagepredictionsinmice AT hartmutgeiger targetedmethodsforepigeneticagepredictionsinmice AT wolfgangwagner targetedmethodsforepigeneticagepredictionsinmice
_version_	1718392489903128576

Targeted methods for epigenetic age predictions in mice

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