Impaired lipid metabolism by age-dependent DNA methylation alterations accelerates aging

Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4328-4336. doi: 10.1073/pnas.1919403117. Epub 2020 Feb 6.

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.

Keywords: ER stress; aging; epigenetic alteration; lipid metabolism; mitochondrial dysfunction.

Publication types

  • Retracted Publication