Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity

Zaijun Ma; Hui Wang; Yuping A. 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

doi:10.7554/elife.35368

Molecular BiologyeLifeMay 29, 2018

Peer-reviewed journal article

Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity

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

Abstract

Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging is unclear. 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. Moreover, we show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis by gene mutation 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 defines a new aging mechanism and that stimulation of glycolysis promotes metabolic health and longevity.

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