TY - JOUR T1 - Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity JF - bioRxiv DO - 10.1101/247726 SP - 247726 AU - Zaijun Ma AU - Hui Wang AU - Yuping Cai AU - Han Wang AU - Kongyan Niu AU - Xiaofen Wu AU - Huanhuan Ma AU - Yun Yang AU - Wenhua Tong AU - Feng Liu AU - Zhandong Liu AU - Yaoyang Zhang AU - Rui Liu AU - Zheng-Jiang Zhu AU - Nan Liu Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/01/15/247726.abstract N2 - 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. ER -