Catalpol extends lifespan through sod-3-mediated mitophagy in Caenorhabditis elegans

Autophagy is an essential process that helps cells maintain balance by breaking down and reusing damaged organelles and abnormal proteins. The decline in its function is widely acknowledged as a significant contributor to aging. Catalpol (CAT), the main active ingredient in Rehmannia root, shows promise for treating age-related diseases by influencing autophagy. However, its specific mechanisms for anti-aging effects are not well understood. This study used Caenorhabditis elegans (C. elegans) as a model organism to explore the role of CAT in mitophagy and to uncover its potential anti-aging mechanisms. Our findings reveal that CAT treatment significantly extends both median and maximum lifespan, maintains muscle mass and viable cell content, improves survival, and attenuates age‑related decline in aging C. elegans. Further analysis indicates that CAT enhances mitochondrial function in these C. elegans through mitophagy, thereby improving their resistance to oxidative stress. Additionally, RNA sequencing and bioinformatics analysis identified SOD-3 as a key target of CAT. Using SOD-3KO strains, we confirmed that CAT improves mitochondrial function and boosts resistance to oxidative stress through SOD-3 dependent mitophagy. In conclusion, our study shows that CAT has anti-aging effects in C. elegans by promoting mitophagy mediated by SOD-3.