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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
doi: https://doi.org/10.1101/247726
Zaijun Ma
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Hui Wang
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Yuping Cai
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Han Wang
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Kongyan Niu
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
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Xiaofen Wu
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Huanhuan Ma
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Yun Yang
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
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Wenhua Tong
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
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Feng Liu
3National Research Center for Translational Medicine (Shanghai), State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Lu, Shanghai, 200025, China
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Zhandong Liu
4Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas 77030, USA
5Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
6Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
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Yaoyang Zhang
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
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Rui Liu
7Singlera Genomics, 781 Cailun Road, Rm 1208, Pudong, Shanghai, 201203, China
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Zheng-Jiang Zhu
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
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  • For correspondence: jiangzhu@sioc.ac.cn liunan@sioc.ac.cn
Nan Liu
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Rd., Pudong, Shanghai, 201210, China
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  • For correspondence: jiangzhu@sioc.ac.cn liunan@sioc.ac.cn
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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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Posted January 15, 2018.
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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
bioRxiv 247726; doi: https://doi.org/10.1101/247726
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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
bioRxiv 247726; doi: https://doi.org/10.1101/247726

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