Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands

Susan J. Broughton, Matthew D. W. Piper, Tomoatsu Ikeya, Timothy M. Bass, Jake Jacobson, Yasmine Driege, Pedro Martinez, Ernst Hafen, Dominic J. Withers, Sally J. Leevers and Linda Partridge

Department of Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom
Zoological Institute, University of Zurich-Irchel, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Centre for Diabetes and Endocrinology, University College London, Rayne Institute, 5, University Street, London WC1E 6J, United Kingdom
Growth Regulation Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.

The insulin/insulin-like growth factor-like signaling pathway, present in all multicellular organisms, regulates diverse functions including growth, development, fecundity, metabolic homeostasis, and lifespan. In flies, ligands of the insulin/insulin-like growth factor-like signaling pathway, the Drosophila insulin-like peptides, regulate growth and hemolymph carbohydrate homeostasis during development and are expressed in a stage- and tissue-specific manner. Here, we show that ablation of Drosophila insulin-like peptide-producing median neurosecretory cells in the brain leads to increased fasting glucose levels in the hemolymph of adults similar to that found in diabetic mammals. They also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold. However, the ablated flies show an extension of median and maximal lifespan and increased resistance to oxidative stress and starvation.