Abstract
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.
Highlights
Fruit flies, which are ectothermic animals, can live more than twice as long at 18°C than at 25°C [1]
To investigate how stress resistance in flies is influenced by the developmental temperatures, we compared the RNA expression levels between 2-day-old male flies developed at 18°C and 25°C by microarray analyses (Fig. 1)
To test if the downregulation of imd (0.76-fold) and antimicrobial peptides (AMPs) genes contributed to higher stress resistance in the flies developed at 18°C (Fig. 1A), we reduced the expression of the imd gene with the hypomorphic imd mutants and compared the stress resistance between the
Summary
Fruit flies, which are ectothermic animals, can live more than twice as long at 18°C than at 25°C [1]. We found that development at 18°C (from embryo to newborn adult) significantly enhances stress resistance of adult flies with more accumulation of nutrients (especially fat) in the body than development at 25°C [3]. This enhanced resistance to stress was observed in both sexes and sustained up to 30 days (middle age) after hatching of the adult flies [3], indicating that development at a lower temperature, 18°C, significantly enhances the mechanism(s) of stress resistance. The Imd pathway is known to regulate innate immune responses in Drosophila [9], and the Imd protein activates two downstream branches, JNK/basket and NF-kB/Relish, which are subsequently responsible for the upregulation of stress tolerance and antimicrobial peptide genes, respectively [10, 11]
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