Insights from a recent study in C. elegans
Childhood is a wondrous time (for most), where you can enjoy freedom from the responsibilities of adulthood. But then, the years start to fly by, and we get wrapped up in our career and family (and paying taxes…). And another birthday flies by, leaving us wondering how to either slow time down or add a few more years to our lives. Fear not because the endocannabinoid system (ECS) is here to save the day — well, at least, if you’re a worm.
A recent study led by Chen et al. (2019) at The Scripps Research Institute evaluated metabolic factors that contribute to the lifespan of Caenorhabditis
elegans, a roundworm commonly used in genetic research. While studies have identified small molecules related to longevity, the mechanisms underlying their actions remained unknown. [1]
Metabolic serine hydrolases (SHs) include over 200 enzymes that break down different substances in the body. [2] Studies have shown that several of these enzymes impact the lifespan of C. elegans. Thus, researchers in this study focused on molecules that block SHs using a technique called phenotypic screening. [1]
This method allows researchers to determine whether small molecules are associated with a particular phenotype, or characteristic. In this case, the phenotype would be lifespan.
“Metabolic processes are very important in determining the rate of aging and lifespan, and serine hydrolases are major metabolic enzymes, so we thought there was a good chance we’d find an important aging-related enzyme this way,” says Alice Chen, first author of the study and graduate student, in a press release.
Phenotypic screening identified a compound called JZL184, which inhibits an enzyme called monoacylglycerol lipase (MAGL). [1] This enzyme breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG). [3] Through additional analyses, fatty acid amide hydrolase-4 (FAAH-4), another member of the SH family, was revealed to be a target of JZL184. FAAH-4 also breaks down 2-AG. In short, here, all roads lead back to endocannabinoids.
Finally, genetic alteration of faah-4 increased 2-AG levels and extended the C. elegans lifespan by approximately 45%. [1] These results suggest that regulators of lipid metabolism significantly impact the ECS and also contribute to longevity. Pretty wild stuff.
So this is great for the worm, but is there any evidence that it could have similar effects in humans?
“It seems at least plausible at this point that both worms and mammals have a cannabinoid-related signaling pathway that affects longevity and possibly aging-related disorders,” said senior author of the study Benjamin Cravatt, PhD, Professor and Gilula Chair of Chemical Biology at Scripps Research.
Due to the intricacies of this molecular pathway, it’s too soon to say whether cannabis could extend your lifespan in any way. While cannabis has many superpowers, increasing longevity may not be supported by the literature – yet.
References
- Chen, A.L., et al. “Pharmacological Convergence Reveals A Lipid Pathway That Regulates C. elegans Lifespan.” Nature Chemical Biology, vol.15, 2019,
pp. 453-462. (impact factor: 12.154; cited by: N/A) - Long, J.Z. & Cravatt, B.F. “The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease.” Chem Rev, vol.111, no.10, 2011, pp. 6022-6063. (impact factor: 52.613; cited by: 202)
- Kerr, D.M., et al. “The Monoacylglycerol Lipase Inhibitor JZL184 Attenuates LPS-induced Increases In Cytokine Expression In The Rat Frontal Cortex And Plasma: Differential Mechanisms of Action.” Br J Pharmacol, vol.169, no.4, 2013, pp. 808-819. (impact factor: 6.81; cited by: 47)
