The Sleeping Beauty: How Reproductive Diapause Affects Hormone Signaling, Metabolism, Immune Response and Somatic Maintenance in <i>Drosophila melanogaster</i>

<div><p>Some organisms can adapt to seasonal and other environmental challenges by entering a state of dormancy, diapause. Thus, insects exposed to decreased temperature and short photoperiod enter a state of arrested development, lowered metabolism, and increased stress resistance. <i>Drosophila melanogaster</i> females can enter a shallow reproductive diapause in the adult stage, which drastically reduces organismal senescence, but little is known about the physiology and endocrinology associated with this dormancy, and the genes involved in its regulation. We induced diapause in <i>D. melanogaster</i> and monitored effects over 12 weeks on dynamics of ovary development, carbohydrate and lipid metabolism, as well as expression of genes involved in endocrine signaling, metabolism and innate immunity. During diapause food intake diminishes drastically, but circulating and stored carbohydrates and lipids are elevated. Gene transcripts of glucagon- and insulin-like peptides increase, and expression of several target genes of these peptides also change. Four key genes in innate immunity can be induced by infection in diapausing flies, and two of these, <i>drosomycin and cecropin A1</i>, are upregulated by diapause independently of infection. Diapausing flies display very low mortality, extended lifespan and decreased aging of the intestinal epithelium. Many phenotypes induced by diapause are reversed after one week of recovery from diapause conditions. Furthermore, mutant flies lacking specific insulin-like peptides (<i>dilp5</i> and <i>dilp2-3</i>) display increased diapause incidence. Our study provides a first comprehensive characterization of reproductive diapause in <i>D. melanogaster</i>, and evidence that glucagon- and insulin-like signaling are among the key regulators of the altered physiology during this dormancy.</p>