Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila
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
Affiliations
Zaijun Ma
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Yuping Cai
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Han Wang
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Kongyan Niu
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China
Xiaofen Wu
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Huanhuan Ma
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Yun Yang
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China; University of Chinese Academy of Sciences, Beijing, China
Wenhua Tong
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China
Feng Liu
National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhandong Liu
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Texas, United States; Department of Pediatrics, Baylor College of Medicine, Houston, United States; Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, United States
Yaoyang Zhang
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Pudong, China
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.
