A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

Abstract

The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.

Population dependent effects of photoperiod on diapause related physiological traits in an invasive beetle (Leptinotarsa decemlineata)

“…It should be stressed that many parts of the regulatory machinery are still very vaguely known, and inter-species variation is large. For instance, the cellular JH receptor still remains unknown and the link between JH titer and Insulin signaling has only been investigated in a handful of studies (Tatar et al 2001, Williams et al 2006, Sim and Denlinger 2008. Therefore many steps are to be taken as hypothetical.…”

Generation and modulation of chemosensory behaviors in C. elegans

“…A key signaling pathway regulating C. elegans lifespan and those of other organisms acts via insulin/IGF signaling [15,[32][33][34][35][36][37]. Mutations that prevent the worm from sensing the environment correctly, such as mutants with defective ciliary structures (see below), or compromised sensory signal transduction, exhibit lengthened lifespan via downregulation of insulin signaling [38,39].…”

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

“…Under laboratory settings, the lifespan of D. melanogaster has been successfully increased by genetic manipulations (Clancy et al., 2001; Hwangbo, Gershman, Tu, Palmer & Tatar, 2004; Kapahi et al., 2004; Lin, Seroude & Benzer, 1998; Orr & Sohal, 1994; Parkes et al., 1998; Sun, Folk, Bradley & Tower, 2002; Tatar et al., 2001), dietary interventions (Chapman & Partridge, 1996; Grandison, Piper & Partridge, 2009; Lee et al., 2014; Magwere, Chapman & Partridge, 2004; Mair, Goymer, Pletcher & Partridge, 2003; Min & Tatar, 2006), and pharmacological treatments (Bjedov et al., 2010; Danilov et al., 2013; Wang et al., 2013). These findings are similar to those reported in other model organisms and highlight the important role of nutrient sensing, mTOR, NAD/sirtuins, insulin/IGF1 signaling pathways, and other systems in lifespan control (Fontana, Partridge & Longo, 2010; He et al., 2014).…”