Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan in Drosophila TAGC 2020

In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one relevant environmental variable is oxygen. In their natural ecology, larvae grow by burrowing into rotting, fermenting food that is rich in microorganisms. This environment is likely low in oxygen and, as a result, Drosophila have evolved mechanisms to tolerate hypoxia. While the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adults is less clear. We have begun exploring this issue. Here we show that Drosophila exposed to hypoxia during their larval period subsequently show reduced starvation stress resistance and shorter lifespan as adults, with these effects being stronger in males. We find that these effects are associated with reduced expression of brain-derived Drosophila insulin-like peptides and a decrease in whole-body insulin signaling. In contrast, we see elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. We find that males, but not females, adults exposed to hypoxia as larvae had elevated levels of lipids and glycogen. Moreover, we see that both males and females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults, which may explain why they are starvation sensitive. Together, these data show how early-life hypoxia can exert persistent long-term effects on Drosophila adult physiology and lifespan. Western blots, qRT-PCR and several metabolic assays were used in this research.