Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity

Zaijun Ma, Hui Wang, Yuping Cai, Han Wang, Kongyan Niu, Xiaofen Wu, Huanhuan Ma, Yun Yang, Wenhua Tong, Feng Liu, Zhandong Liu, Yaoyang Zhang, Rui Liu, Zheng-Jiang Zhu, Nan Liu

Preprint posted on 15 January 2018

Article now published in eLife at

Do epigenetic changes contribute to aging? A recent preprint shows that histone H3K27 methylation is a critical determinant of longevity in flies.

Selected by Sammi (Shuang Wang)

Categories: molecular biology

Summary of the preprint

In the current study, Ma et al. combined genome-wide histone profiling with powerful fly genetics to identify age-associated changes in H3K27me3 as a critical determinant of longevity and organismal fitness. The authors first made the interesting observation that, just like in mammals, aging flies display an overall increase in H3K27me3, especially in the regions that have low methylation levels in younger animals. Using genetically modified flies with altered levels of H3K27me3, the authors demonstrated that the level of H3K27me3 was inversely proportional to longevity, providing strong support for the global increase in H3K27me3 as a driver of the aging process. Furthermore, the authors discovered that increased H3K27me3 contributes to aging through a selective inhibition of glycolytic genes, which in turn altered glucose metabolism and redox state that accelerated aging. The authors’ findings are summarized in the diagram below extracted from figure 7 of their preprint.

Why this preprint caught my eye

Epigenetic changes have long been associated with aging; in fact, DNA methylation profiling provides one of the best predictors of biological age in both human and mouse (Hannum et al. ; Stubbs et al. 2017). Whether such epigenetic changes represent a driver or merely a passenger of the aging process remains unclear. Taking a genomic approach that linked global changes in H3K27me3 patterning to glycolysis, this study unequivocally established age-related changes in the epigenome, which is observed across the phylogenetic tree, as a driver of the aging process.

Open questions

Several interesting questions arise from this study: Why do global changes in H3K27me3 selectively target glycolytic and redox genes, yet spare the more canonical polycomb targets such as the Hox gene family? Can EZH2 (a H3K27 methyltransferase) inhibitors that are currently in clinical trials increase longevity by preventing age-associated changes in H3K27me3 and glycolytic genes? Considering that similar shifts in metabolism occur in cancer, how might results from this aging study contribute to our understanding of the link between epigenetics, aging, and cancer?

( Reproduced from Ma et al.)

Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan J-B, Gao Y et al. Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular Cell 49: 359-367.

Stubbs TM, Bonder MJ, Stark A-K, Krueger F, von Meyenn F, Stegle O, Reik W. 2017. Multi-tissue DNA methylation age predictor in mouse. Genome Biology 18: 68.


Posted on: 19 February 2018 , updated on: 20 February 2018

Read preprint (No Ratings Yet)

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the molecular biology category:

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23


List by Alex Eve

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.


List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.


List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.


List by Nadja Hümpfer et al.

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020


List by Ana Dorrego-Rivas

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome


List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds


This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.


List by Sandra Franco Iborra