Session 1C: Inaugural Lectures by Fellows/Associates

Swagata Dasgupta

Iron-depleted diet enhances the lifespan of Caenorhabditis elegans

Aging is a multifaceted phenomenon characterized by progressive physiological deterioration and is associated with various disorders, such as cancer, diabetes, and neurodegenerative diseases. Recent studies have highlighted the significance of gut microbiota in influencing host health and lifespan. Additionally, host lipid metabolism appears to play a role in aging and age-related disorders. However, the role of the gut microbiota in regulating host lipid metabolism that can impact aging remains understudied. In their study, using host lipid metabolism as a proxy, the speaker and his group screened a genome-wide Escherichia coli mutant library and discovered 26 E. coli mutants that increase Caenorhabditis elegans lifespan. Transcriptomic analysis of worms fed on these E. coli mutants revealed an increase in oxidative stress response genes. We determined that C. elegans fed on these E. coli mutants exhibited increased activity of the mitochondrial unfolded protein response (mt-UPR). The increased mt-UPR and enhanced lifespan were due to reduced iron levels in the identified bacterial mutants. Supplementation with ferric chloride rescued the enhanced mt-UPR and abolished the lifespan extension of worms grown on these diets. Mechanistically, that lifespan enhancement on a low-iron diet is dependent on the HLH-30 and AMP kinase AAK-2 signaling pathways of the host, will be demonstrated.