Ellagic Acid Enhances Longevity and Healthspan in Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway

The role of ellagic acid (EA), a natural antioxidant, in regulating anti-aging and its underlying mechanisms remains unclear. In this study, we investigated the anti-aging effects and molecular mechanisms of EA in Caenorhabditis elegans (C. elegans). Our results demonstrate that EA extends the lifespan of C. elegans, enhances motility, reduces lipofuscin accumulation, and improves overall healthspan. Additionally, EA reduces reactive oxygen species (ROS) accumulation in C. elegans under conditions of heat and oxidative stress. The insulin/IGF-1 signaling (IIS) pathway, a key regulator of longevity and stress resistance in C. elegans, was found to mediate EA's effects. EA treatment did not extend the lifespan of mutants defective in daf-2, daf-16, hsf-1, hlh-30, and skn-1, confirming that EA's lifespan-extending effect operates through the IIS pathway. Furthermore, EA treatment increased the expression of stress response genes downstream of the IIS pathway. Based on RNA sequencing data, we further explored the molecular mechanisms and potential regulatory roles of EA in anti-aging. Overall design: EA C. elegans