1. Developmental Biology
  2. Genetics and Genomics
Download icon

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
Tools and Resources
  • Cited 15
  • Views 4,214
  • Annotations
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.

Data availability

Raw data of pyrosequencing is provided as supplemental EXCEL table (Source data 1).

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: April 13, 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.

Metrics

  • 4,214
    Page views
  • 609
    Downloads
  • 15
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Alessandro Bonfini et al.
    Research Article

    The gut is the primary interface between an animal and food, but how it adapts to qualitative dietary variation is poorly defined. We find that the Drosophila midgut plastically resizes following changes in dietary composition. A panel of nutrients collectively promote gut growth, which sugar opposes. Diet influences absolute and relative levels of enterocyte loss and stem cell proliferation, which together determine cell numbers. Diet also influences enterocyte size. A high sugar diet inhibits translation and uncouples ISC proliferation from expression of niche-derived signals but, surprisingly, rescuing these effects genetically was not sufficient to modify diet's impact on midgut size. However, when stem cell proliferation was deficient, diet's impact on enterocyte size was enhanced, and reducing enterocyte-autonomous TOR signaling was sufficient to attenuate diet-dependent midgut resizing. These data clarify the complex relationships between nutrition, epithelial dynamics, and cell size, and reveal a new mode of plastic, diet-dependent organ resizing.

    1. Developmental Biology
    2. Physics of Living Systems
    Yonghyun Song, Changbong Hyeon
    Research Article Updated

    Spatial boundaries formed during animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. The accuracy of boundary location is limited by the fluctuations of morphogen concentration that thresholds the expression level of target gene. Producing more morphogen molecules, which gives rise to smaller relative fluctuations, would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost. In the classical diffusion-depletion model of morphogen profile formation, the morphogen molecules synthesized from a local source display an exponentially decaying concentration profile with a characteristic length λ. Our theory suggests that in order to attain a precise profile with the minimal cost, λ should be roughly half the distance to the target boundary position from the source. Remarkably, we find that the profiles of morphogens that pattern the Drosophila embryo and wing imaginal disk are formed with nearly optimal λ. Our finding underscores the cost-effectiveness of precise morphogen profile formation in Drosophila development.