Stress resistance and lifespan enhanced by downregulation of antimicrobial peptide genes in the Imd pathway

Biological behaviors and longevity of ectothermic animals are remarkably influenced by ambient temperature. Development at 18°C significantly enhances the stress resistance of adult flies with more accumulation of nutrients (especially fat) in the body than development at 25°C. Gene expression analysis between the flies developed at 18°C and 25°C revealed that the Immune deficiency (Imd) pathway, including the downstream antimicrobial peptides (AMPs), is downregulated in the flies developed at 18°C. When hypomorphic imd mutant flies with reduced AMP expressions were developed at 25°C, they showed induced stress resistance with higher fat content in the body similar to the wild-type flies developed at 18°C. However, severe hypomorphic imd mutants could not enhance stress resistance due to the downregulation of another downstream JNK pathway that expresses stress tolerance genes. Interestingly, the downregulation of AMP genes, itself, extended lifespan with increased stress resistance. Especially, fat body-specific downregulation of Imd AMP genes exhibited a longer lifespan with higher heat resistance. The fat body is known to function in metabolic homeostasis, stress tolerance, growth, and longevity in Drosophila. Here, we provide the first evidence that mild downregulation of the Imd pathway with AMP genes increases fat content, stress resistance, and lifespan in adult flies.