ArticleNature chemical biology2019
Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans.GeroScience · 2024Review
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana.Neurochemical research · 2024Article
- Multiple Targets, One Goal: Compounding life-extending effects through Polypharmacology.bioRxiv : the preprint server for biology · 2024Article
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana.Research square · 2024Article
- Quantifying Food Intake in Caenorhabditis elegans by Measuring Bacterial Clearance.Journal of visualized experiments : JoVE · 2024Article
- Icariin Improves Stress Resistance and Extends Lifespan inInternational journal of molecular sciences · 2023Article
- A robotic system for automated genetic manipulation and analysis ofPNAS nexus · 2023Article
- Two legume fatty acid amide hydrolase isoforms with distinct preferences for microbial- and plant-derived acylamides.Scientific reports · 2023Article
- Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids.Nature cell biology · 2023Article
- The Endocannabinoid System in Caenorhabditis elegans.Reviews of physiology, biochemistry and pharmacology · 2023Review
- Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans.PLoS genetics · 2022Article
- Lipid metabolism and ageing in Caenorhabditis elegans: a complex interplay.Biogerontology · 2022Review
- Comprehensive evaluation of chemical composition and health-promoting effects with chemometrics analysis of plant derived edible oils.Food chemistry: X · 2022Article
- CEST-2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants.EMBO reports · 2022Article
- Anti-Obesity Efficacy ofInternational journal of molecular sciences · 2022Article
- Pioglitazone Hydrochloride Extends the Lifespan ofOxidative medicine and cellular longevity · 2022Article
- Review
- Combinatorial Assembly of Modular Glucosides via Carboxylesterases RegulatesJournal of the American Chemical Society · 2021Article
- Lipid metabolism and lipid signals in aging and longevity.Developmental cell · 2021Review
- A Superfamily-wide Activity Atlas of Serine Hydrolases inBiochemistry · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Phenotypic screening has identified small-molecule modulators of aging, but the mechanism of compound action often remains opaque due to the complexities of mapping protein targets in whole organisms. Here, we combine a library of covalent inhibitors with activity-based protein profiling to coordinately discover bioactive compounds and protein targets that extend lifespan in Caenorhabditis elegans. We identify JZL184-an inhibitor of the mammalian endocannabinoid (eCB) hydrolase monoacylglycerol lipase (MAGL or MGLL)-as a potent inducer of longevity, a result that was initially perplexing as C. elegans does not possess an MAGL ortholog. We instead identify FAAH-4 as a principal target of JZL184 and show that this enzyme, despite lacking homology with MAGL, performs the equivalent metabolic function of degrading eCB-related monoacylglycerides in C. elegans. Small-molecule phenotypic screening thus illuminates pure pharmacological connections marking convergent metabolic functions in distantly related organisms, implicating the FAAH-4/monoacylglyceride pathway as a regulator of lifespan in C. elegans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.