| Literature DB >> 32029582 |
Xin Li1, Jiaqiang Wang2, Leyun Wang2, Guihai Feng2, Gen Li3,4, Meixin Yu3,4, Yufei Li2, Chao Liu2, Xuewei Yuan2, Guangxi Zang5, Zhihuan Li5, Ling Zhao6, Hong Ouyang6, Qingli Quan3,4, Guangyu Wang7, Charlotte Zhang5, Oulan Li5, Junkai Xiang4, Jian-Kang Zhu8,9, Wei Li10, Qi Zhou10, Kang Zhang11.
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.Entities:
Keywords: ER stress; aging; epigenetic alteration; lipid metabolism; mitochondrial dysfunction
Year: 2020 PMID： 32029582 PMCID： PMC7049154 DOI： 10.1073/pnas.1919403117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205