1. Developmental Biology
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Epigenetic age-predictor for mice based on three CpG sites

  1. Yang Han
  2. Monika Eipel
  3. Julia Franzen
  4. Vadim Sakk
  5. Bertien Dethmers-Ausema
  6. Laura Yndriago
  7. Ander Izeta
  8. Gerald de Haan
  9. Hartmut Geiger
  10. Wolfgang Wagner  Is a corresponding author
  1. RWTH Aachen University Medical School, Germany
  2. University of Ulm, Germany
  3. University Medical Center Groningen, Netherlands
  4. Instituto Biodonostia, Spain
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Cite this article as: eLife 2018;7:e37462 doi: 10.7554/eLife.37462

Abstract

Epigenetic clocks for mice were generated based on deep-sequencing analysis of the methylome. Here, we demonstrate that site-specific analysis of DNA methylation levels by pyrosequencing at only three CG dinucleotides (CpGs) in the genes Prima1, Hsf4, and Kcns1 facilitates precise estimation of chronological age in murine blood samples, too. DBA/2 mice revealed accelerated epigenetic aging as compared to C57BL6 mice, which is in line with their shorter life-expectancy. The three-CpG-predictor provides a simple and cost-effective biomarker to determine biological age in large intervention studies with mice.

Article and author information

Author details

  1. Yang Han

    Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany
    Competing interests
    No competing interests declared.
  2. Monika Eipel

    Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany
    Competing interests
    No competing interests declared.
  3. Julia Franzen

    Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany
    Competing interests
    No competing interests declared.
  4. Vadim Sakk

    Instituts of Molecular Medicine, University of Ulm, Ulm, Germany
    Competing interests
    No competing interests declared.
  5. Bertien Dethmers-Ausema

    Laboratory of Ageing Biology and Stem Cells, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  6. Laura Yndriago

    Tissue Engineering Laboratory, Instituto Biodonostia, San Sebastian, Spain
    Competing interests
    No competing interests declared.
  7. Ander Izeta

    Tissue Engineering Laboratory, Instituto Biodonostia, San Sebastian, Spain
    Competing interests
    No competing interests declared.
  8. Gerald de Haan

    Laboratory of Ageing Biology and Stem Cells, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9706-0138
  9. Hartmut Geiger

    Institute of Molecular Medicine, University of Ulm, Ulm, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5794-5430
  10. Wolfgang Wagner

    Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany
    For correspondence
    wwagner@ukaachen.de
    Competing interests
    Wolfgang Wagner, is cofounder of Cygenia GmbH that can provide service for Epigenetic-Aging-Signatures (www.cygenia.com), but the method is fully described in this manuscript..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1971-3217

Funding

Else Kröner-Fresenius-Stiftung (2014_A193)

  • Wolfgang Wagner

Deutsche Forschungsgemeinschaft (SFBs 1275)

  • Hartmut Geiger

NIH Clinical Center (R01DK104814)

  • Hartmut Geiger

Bundesministerium für Bildung und Forschung (SyStarR)

  • Hartmut Geiger

Deutsche Forschungsgemeinschaft (DFG; WA 1706/8-1)

  • Wolfgang Wagner

Bundesministerium für Bildung und Forschung (BMBF; 01KU1402B)

  • Wolfgang Wagner

NIH Clinical Center (R01HL134617)

  • Hartmut Geiger

Netherland Organization for Scientific Research

  • Gerald de Haan

Deutsche Forschungsgemeinschaft (GRK 1789 CEMMA)

  • Hartmut Geiger

Deutsche Forschungsgemeinschaft (GRK 2254 HEIST)

  • Hartmut Geiger

Deutsche Forschungsgemeinschaft (SFBs 1074)

  • Hartmut Geiger

Deutsche Forschungsgemeinschaft (SFBs 1149)

  • Hartmut Geiger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were approved by the Institutional Animal Care of the Ulm University as well as by Regierungspräsidium Tübingen and by the Institutional Animal Care and Use Committee of the University of Groningen (IACUC-RUG), respectively....To analyze age-associated changes in different tissues we used 3 young (67 days old) and 3 old (398 days old) C57BL/6J mice (JaxMice) in accordance with relevant Spanish and European guidelines after approval by the Biodonostia Animal Care Committee.

Reviewing Editor

  1. Vadim N Gladyshev, Brigham and Women's Hospital, Harvard Medical School, United States

Publication history

  1. Received: May 3, 2018
  2. Accepted: August 23, 2018
  3. Accepted Manuscript published: August 24, 2018 (version 1)
  4. Version of Record published: September 25, 2018 (version 2)

Copyright

© 2018, Han et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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