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Targeted methods for epigenetic age predictions in mice.

Yang Han1,2, Miloš Nikolić1,2, Michael Gobs1,2

  • 1Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.

Scientific Reports
|January 1, 2021
PubMed
Summary

New methods using droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq) offer novel ways to predict biological age in mice. These epigenetic clocks reveal accelerated aging in specific mouse strains, aiding aging research.

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Area of Science:

  • Epigenetics
  • Gerontology
  • Molecular Biology

Background:

  • DNA methylation patterns change with age, serving as a biomarker for biological aging.
  • Epigenetic clocks in mice are valuable tools for studying aging influenced by genetics and treatments.
  • Previous methods included genome-wide profiles and targeted pyrosequencing of specific DNA methylation regions.

Purpose of the Study:

  • To establish and evaluate alternative targeted methods for epigenetic age prediction in mice.
  • To compare the efficacy of droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq) with existing methods.
  • To investigate epigenetic aging heterogeneity and its correlation with lifespan in different mouse strains.

Main Methods:

  • Development of targeted assays using ddPCR and BBA-seq for DNA methylation analysis.
  • Correlation analysis of DNA methylation at individual CpGs (cytosine-guanine dinucleotides) with chronological age.
  • Assessment of stochastic methylation patterns in neighboring CpGs using BBA-seq.
  • Single-read age prediction to explore epigenetic aging heterogeneity.
  • Comparison of age predictions between C57BL/6 and DBA/2 mice, and genetically modified C57BL/6 mice.

Main Results:

  • Both ddPCR and pyrosequencing showed a slightly higher correlation of DNA methylation with age at individual CpGs compared to BBA-seq.
  • BBA-seq identified stochastic modification of neighboring CpGs in murine age-associated regions.
  • Single-read predictions from BBA-seq revealed accelerated epigenetic aging in shorter-lived DBA/2 mice and in C57BL/6 mice carrying DBA/2 lifespan QTLs.
  • Epigenetic age predictions using BBA-seq reflected differences in aging rates between mouse strains.

Conclusions:

  • ddPCR and BBA-seq provide viable alternative targeted methods for epigenetic age prediction in mice.
  • BBA-seq offers insights into stochastic methylation and epigenetic aging heterogeneity at the single-read level.
  • These methods enhance the study of aging interventions and genetic influences on aging in mouse models.