bioRxiv Science⌕ Search

Biology subjects

Polan, D. M.

Publications and source records attributed to Polan, D. M..

2 recordsLinked to original sources

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

In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia. Drosophila larvae live on rotting, fermenting food rich in microorganisms - an environment characterized by low ambient oxygen. They have therefore evolved to tolerate hypoxia. While the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness is less clear. 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 whole-body insulin signaling but 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. Thus, we find that males, but not females, showing 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. These data show how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on Drosophila adult physiology and lifespan.

physiology↗

FOXO mediates organismal hypoxia tolerance by regulating NF-κB in Drosophila

Exposure of tissues and organs to low oxygen (hypoxia) occurs in both physiological and pathological conditions in animals. Under these conditions, organisms have to adapt their physiology to ensure proper functioning and survival. Here we define a role for the transcription factor FOXO as a mediator of hypoxia tolerance in Drosophila. We find that upon hypoxia exposure, FOXO transcriptional activity is rapidly induced in both larvae and adults. Moreover, we see that foxo mutant animals show misregulated glucose metabolism in low oxygen and subsequently exhibit reduced hypoxia survival. We identify the innate immune transcription factor, NF-KappaB/Relish, as a key FOXO target in the control of hypoxia tolerance. We find that expression of Relish and its target genes are increase in a FOXO-dependent manner in hypoxia, and that relish mutant animals show reduced survival in hypoxia. Together, these data indicate that FOXO is a hypoxia inducible factor that mediates tolerance to low oxygen by inducing immune-like responses.

cell biology↗