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

Abstract

18In many animals, short-term fluctuations in environmental conditions in early life often exert long-term 19 effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia. 20 Drosophila larvae live on rotting, fermenting food rich in microorganisms -an environment characterized 21 by low ambient oxygen. They have therefore evolved to tolerate hypoxia. While the acute effects of 22 hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness 23 is less clear. Here we show that Drosophila exposed to hypoxia during their larval period subsequently 24 show reduced starvation stress resistance and shorter lifespan as adults, with these effects being 25 stronger in males. We find that these effects are associated with reduced whole-body insulin signaling 26 but elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually 27 dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. Thus, we find that males, 28 but not females, showing elevated levels of lipids and glycogen. Moreover, we see that both males and 29 females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults. 30 These data show how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on 31 Drosophila adult physiology and lifespan. 32 33 34 35Animals often live in conditions where environmental conditions such as temperature, food, oxygen, 36 and pathogen exposure, can fluctuate dramatically. The ability of animals to adapt their metabolism and 37 physiology to these changing environments is essential for their survival. Many adaptive responses 38 occur immediately in response to changes in environment, particularly in response to environmental 39 stressors (e.g. starvation, hypoxia, infection), to allow animals to survive whilst subjected to these stress 40 conditions. It is also increasingly appreciated that acute, early-life environmental stresses can trigger 41 longer-term responses that can influence later adult physiology and fitness (Gluckman and Hanson, 42

The early‐life stress induced by oxytocin inhibition in p53 knockout mouse dams increases adulthood tumorigenesis in first and second generations

“…Early life is a critical time period for all species as somatic and germ cells complete development and unfavorable events such as nutrient, 33 heat or oxygen 34 deprivation can have long‐term consequences, possibly inheritable from one generation to the next one 35 . In humans, adverse conditions during early life have been found to favor several disorders including obesity, 36 cognitive dysfunctions, 30 inflammation, 37 and to increase the incidence of life‐threatening cardiovascular diseases and cancer 38 .…”