ISSN 1662-4009 (online)

ey0021.15-16 | New Paradigms | ESPEYB21

15.16. Causality-enriched epigenetic age uncouples damage and adaptation

K Ying , H Liu , AE Tarkhov , MC Sadler , AT Lu , M Moqri , S Horvath , Z Kutalik , X Shen , VN. Gladyshev

In Brief: The authors harness large-scale genetic and DNA methylation datasets in an epigenome-wide Mendelian randomization approach, to identify CpG sites that appear to be causally related to aging-related traits. These sites are collated to produce 2 epigenetic clocks: DamAge has adverse impacts on age-related outcomes, including mortality. AdaptAge appears to confer beneficial adaptations.Steve Horvath and others originally described various epigenet...

ey0017.15-11 | (1) | ESPEYB17

15.11. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

B Chaurasia , TS Tippetts , R Mayoral Monibas , J Liu , Y Li , L Wang , JL Wilkerson , CR Sweeney , RF Pereira , DH Sumida , JA Maschek , JE Cox , V Kaddai , GI Lancaster , MM Siddique , A Poss , M Pearson , S Satapati , H Zhou , DG McLaren , SF Previs , Y Chen , Y Qian , A Petrov , M Wu , X Shen , J Yao , CN Nunes , AD Howard , L Wang , MD Erion , J Rutter , WL Holland , DE Kelley , SA Summers

To read the full abstract: Science 2019;365:386–392.By genetically engineering mice, the authors deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets<p c...