Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila
- Chinese Academy of Sciences, China
- Shanghai Jiao Tong University School of Medicine, China
- Texas Children's Hospital, United States
- Singlera Genomics, China
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.
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Raw data of sequencing experiments, normalized read density profiles of ChIP-seq, and the differential expression results from DESeq of RNA-seqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE96654).
Article and author information
Author details
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.
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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Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila
eLife 7:e35368.
https://doi.org/10.7554/eLife.35368
