Impaired lipid metabolism by age-dependent DNA methylation alterations accelerates aging
- 6 February 2020
- journal article
- retracted article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (8), 4328-4336
- https://doi.org/10.1073/pnas.1919403117
Abstract
Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism. Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction, leading to key accelerated aging phenotypes. Restoration of mitochondrial activity can rescue age-related macular degeneration (AMD) phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial (RPE) cells. We revealed an epigenetic–metabolism axis contributing to aging and potentially to antiaging therapy.Funding Information
- Chinese Academy of Sciences, Strategic Priority Research Program (XDA16030400)
- National Natural Science Foundation of China (31621004)
- National Natural Science Foundation of China (31471395)
- National Natural Science Foundation of China (31701286)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (NA)
- Chinese Academy of Sciences Key Project (QYZDY-SSW-SMC002)
- Key Deployment Projects of the Chinese Academy of Sciences (ZDRW-ZS-2017-4)
- National Basic Research Program of China (2014cB964801)
- China Postdoctoral Science Foundation (2017M610990 and 2017T100107)
- China National Postdoctoral Program for Innovative Talents (BX201700243)
- National key research and development program (2017YFA0103803)
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