Abstract: Objective: The aim of this study was to determine the effect of bitter melon saponin (BMS) on the lifespan of Caenorhabditis elegans and its correlation with the lipid-lowering effect of BMS. Methods: The effect of BMS (50, 100 and 200 μg/mL) on fat deposition in C. elegans was analyzed by oil red O staining and triglyceride (TG) assay. The impacts of BMS on the basic physiological activities of C. elegans were evaluated by measuring body length, body width, locomotive activity and lifespan. The mRNA expression levels of lipid metabolism-related genes were detected by quantitative real-time polymerase chain reaction (qPCR). By using C. elegans mutants deficient in lipid metabolism-related genes, the relationship between the regulatory effect of BMS on the lifespan of C. elegans and its lipid metabolism was established. Results: 100 and 200 μg/mL BMS treatment could significantly reduce the TG level (P < 0.05), prolong the natural lifespan of C. elegans (P < 0.000 1) without changing basic physiological activities such as body size and locomotive ability. The mRNA expression levels of nhr-80, fat-5, fat-6 and fat-7 were significantly decreased by treatment with 100 μg/mL BMS (P < 0.05), while the mRNA expression levels of genes related to fatty acid oxidation or lipolysis were not affected. BMS treatment did not significantly extend the lifespan of the single or double mutants deficient in the fat-6 or/and fat-7 genes (P > 0.05). Conclusion: The effect of BMS on prolonging the natural lifespan of C. elegans is closely related to its efficacy in reducing fat deposition, and the mechanism is mainly inhibiting the expression of the two genes encoding desaturases, fat-6 and fat-7.

Key words: Caenorhabditis elegans; bitter melon saponin; fat deposition; lifespan; aging