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

Broughton, Susan J and Piper, Matthew D W and Ikeya, Tomoatsu and Bass, Timothy M and Jacobson, Jake and Driege, Yasmine and Martinez, Pedro and Hafen, Ernst and Withers, Dominic J and Leevers, Sally J and Partridge, Linda (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proceedings of the National Academy of Sciences of the United States of America, 102 (8). pp. 3105-3110. ISSN 0027-8424

Abstract

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.