Objectives: Coffee is one of the most widely consumed beverages and can deliver many beneficial effects on human health. Previous studies have reported that kahweol, a diterpene found in coffee, reduced body fat accumulation via the daf-16-dependent mechanism in Caenorhabditis elegans. C. elegans is a eukaryotic and multi-organ nematode with a short lifecycle and lifespan. It uses a non-pathogenic bacterial strain of E. coli OP50 as a food source and is easy to handle in lab. Based on its genetic properties, 65% of homologs with disease-related genes in humans, C. elegans is widely used in life science research and is considered the premier in vivo model for aging research. In C. elegans, daf-2 encodes insulin/insulin-like growth factor-1 receptor, and daf-16 is its major downstream target, the homolog of the Forkhead box O transcription factor. It is well-known that daf-2 and daf-16 play a major role in the modulation of lifespan; thus, we investigated if the lifespan of C. elegans is regulated by kahweol.
Methods: Lifespan assay was performed using C. elegans strains: N2, Bristol (wild-type), daf-16(mgDf50) I, daf-2(e1307) III, sir-2.1(ok434) IV, eat-2(ad1116) II, and skn-1(mg570) IV. E. coli OP50 was used as food source and 25 µM kahweol was treated to treatment group.
Results: The lifespan of wild-type C. elegans was significantly increased with the treatment of kahweol at 25 µM compared to the control; the average lifespan was increased by 35% (p < 0.0001), and the median lifespan was increased by 33% (p < 0.0001). Both daf-2 and daf-16 null mutants failed to increase lifespan by kahweol treatment compared to the control, which suggests that the extension of lifespan by kahweol mediates the daf-2- and daf-16-dependent pathway. However, the treatment of kahweol significantly increased the lifespan over the control in sir-2.1 (the homolog of NAD-dependent deacetylase sirtuin-1), skn-1 (the homolog of nuclear factor erythroid 2-related factor 2), and eat-2 (the homolog of cholinergic receptor nicotinic alpha 7 subunit with reduced food intake phenotype) mutants.
Conclusions: These results indicate that the insulin/insulin-like growth factor-1 signaling pathway plays a key role in extending lifespan by kahweol in C. elegans.
Funding Sources: This material is based upon work supported in part by U.S. Department of Agriculture and the Massachusetts Agricultural Experiment Station.
