The Anti-Aging Effect of Metformin on C. elegans Through Idha-1, an Isocitrate Dehydrogenase in the TCA Cycle

Global population aging is a hot topic in the 21stcentury, and it drives demand for anti-aging interventions. However, there are no proven anti-aging drugs available, and there are also ethical and practical challenges in testing anti-aging compounds in humans. In this case, Caenorhabditis elegans (C.elegans) serves as a powerful model to study aging due to genetic similarities with humans and short lifespans. In this study, we tested the effect of four compounds (metformin, rapamycin, royal jelly, and rilmenidine) on C. elegans aging. Metformin and rapamycin significantly extended lifespan by 30% and 23%, respectively. Meanwhile, metformin uniquely enhanced the pumping rate, indicating slowed aging. Among the aging-related pathways in C. elegans, the metabolic genes play a vital function. To test the mechanism of metformin in slowing aging, we analyzed the aging-related metabolic genes with RT-qPCR. Metformin was demonstrated to upregulate the expression of the metabolic gene, isocitrate dehydrogenase alpha-1 (idha-1), potentially by elevating the tolerance to oxidative stress. Results highlight idha-1 as a key target for anti-aging interventions.