Summary of project PR002813

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002813. The data can be accessed directly via it's Project DOI: 10.21228/M82554 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR002813
Project DOI:doi: 10.21228/M82554
Project Title:The eicosanoid cascade promotes inflammaging in C. elegans: Quantification of oxylipins in C. elegans following knockout of CEEH-1
Project Summary:Chronic inflammation is a hallmark of aging, but the underlying mechanisms of how inflammatory signaling drives aging remain unclear. Inflammation is in part controlled by the lipid-based eicosanoid signaling cascade consisting of three branches defined by their lipid-metabolizing enzymes, namely cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYPs) enzymes. In an unbiased small molecule screen for lifespan extension in C. elegans, we identify the sulfonyl fluoride SF-3 and show it to extend lifespan by inhibiting soluble epoxide hydrolase 1 (CEEH-1) of C. elegans, a key enzyme in the CYP branch of the eicosanoid cascade. In C. elegans, the hydrolysis of epoxy fatty acids by CEEH-1 generates toxic dihydroxyeicosanoids (DiHETs) that shorten lifespan by the chronic activation of the ATF-6 arm of the UPRER. Our results causally link the CYP branch of the eicosanoid cascade to aging via the hydrolysis of epoxides into DiHETs, some of which are toxic and thus provide a mechanism for how inflammatory signaling drives aging.
Institute:Scripps Research Institute
Department:Molecular and Cellular Biology
Laboratory:Petrascheck
Last Name:Clay
First Name:Khalyd
Address:10550 N. Torrey Pines Rd., La Jolla, Ca, 92037, USA
Email:khalydc@scripps.edu
Phone:9283698108

Summary of all studies in project PR002813

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ST004453 The eicosanoid cascade promotes inflammaging in C. elegans Caenorhabditis elegans Scripps Research Institute MS 2026-01-12 1 30 Uploaded data (19.5M)*
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