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, mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition), 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.