1. Cell Biology
  2. Chromosomes and Gene Expression
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Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila

  1. Zaijun Ma
  2. Hui Wang
  3. Yuping Cai
  4. Han Wang
  5. Kongyan Niu
  6. Xiaofen Wu
  7. Huanhuan Ma
  8. Yun Yang
  9. Wenhua Tong
  10. Feng Liu
  11. Zhandong Liu
  12. Yaoyang Zhang
  13. Rui Liu
  14. Zheng-Jiang Zhu  Is a corresponding author
  15. Nan Liu  Is a corresponding author
  1. Chinese Academy of Sciences, China
  2. Shanghai Jiao Tong University School of Medicine, China
  3. Texas Children's Hospital, United States
  4. Singlera Genomics, China
Research Article
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Cite this article as: eLife 2018;7:e35368 doi: 10.7554/eLife.35368

Abstract

Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. We show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging and that stimulation of glycolysis promotes metabolic health and longevity.

Data availability

The raw data files of sequencing experiments have been deposited in the NCBI Gene Expression Omnibus, as well as the normalized read density profiles of ChIP-seq and differential expression results from DESeq of RNA-seq reported in this paper. The accession number is GEO: GSE96654.

The following data sets were generated

Article and author information

Author details

  1. Zaijun Ma

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  2. Hui Wang

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3522-0164
  3. Yuping Cai

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  4. Han Wang

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  5. Kongyan Niu

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  6. Xiaofen Wu

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  7. Huanhuan Ma

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  8. Yun Yang

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  9. Wenhua Tong

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  10. Feng Liu

    State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    No competing interests declared.
  11. Zhandong Liu

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  12. Yaoyang Zhang

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    No competing interests declared.
  13. Rui Liu

    Singlera Genomics, Shanghai, China
    Competing interests
    Rui Liu, is affiliated with Singlera Genomics, a company providing customized next generation sequencing services. The author has no financial interests to declare.
  14. Zheng-Jiang Zhu

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    jiangzhu@sioc.ac.cn
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3272-3567
  15. Nan Liu

    Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    liunan@sioc.ac.cn
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7384-0794

Funding

National Program on Key Research Projects of China (2016YFA0501900)

  • Nan Liu

National Science Foundation of China (31371326)

  • Nan Liu

National Science Foundation of China (31671428)

  • Yaoyang Zhang

National Science Foundation of China (31500665)

  • Yaoyang Zhang

National Science Foundation of China (31530041)

  • Yaoyang Zhang

National Science Foundation of China (81770143)

  • Feng Liu

National Institutes of Health (GM120033)

  • Zhandong Liu

National Science Foundation (DMS-1263932)

  • Zhandong Liu

Cancer Prevention and Research Institute of Texas (RP170387)

  • Zhandong Liu

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

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Publication history

  1. Received: January 24, 2018
  2. Accepted: April 23, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 7, 2018 (version 2)
  5. Version of Record updated: October 11, 2018 (version 3)

Copyright

© 2018, Ma 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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