Toward the discovery of life assurance genes, we are performing a screen for extended lifespan in Drosophila melanogaster by single gene mutations. The mutant line methuselah consistently displays an approximately 40 percent increase in average lifespan. Interestingly, the mutant flies also show enhanced resistance to conditions of stress, including starvation, low humidity, and high temperature. Upon exposure to paraquat, a free radical generator, they survive longer than control flies. Excision, along with adjacent DNA, results in embryonic lethality in homozygotes, suggesting that the gene also plays an important role during development. The gene structure predicts a protein sequence containing seven hydrophobic regions with homology to various G-protein-coupled, seven-transmembrane-domain cell receptors. This finding suggests that Drosophila can use signal transduction pathways to modulate stress response and aging. This project is to analyze the mechanism involved in methuselah, and to undertake an expanded project for the isolation and analysis of additional life assurance genes.
| Carvalho, Gil B; Ja, William W; Benzer, Seymour (2009) Non-lethal PCR genotyping of single Drosophila. Biotechniques 46:312-4 |
| Ja, William W; Carvalho, Gil B; Zid, Brian M et al. (2009) Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan. Proc Natl Acad Sci U S A 106:18633-7 |
| Ja, William W; Carvalho, Gil B; Madrigal, Marisol et al. (2009) The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. Protein Sci 18:2203-8 |
| Heo, Jiyoung; Ja, William W; Benzer, Seymour et al. (2008) The predicted binding site and dynamics of peptide inhibitors to the Methuselah GPCR from Drosophila melanogaster. Biochemistry 47:12740-9 |
| Ja, William W; West Jr, Anthony P; Delker, Silvia L et al. (2007) Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor. Nat Chem Biol 3:415-9 |
| Ja, William W; Carvalho, Gil B; Mak, Elizabeth M et al. (2007) Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A 104:8253-6 |
| Carvalho, Gil B; Kapahi, Pankaj; Anderson, David J et al. (2006) Allocrine modulation of feeding behavior by the Sex Peptide of Drosophila. Curr Biol 16:692-6 |
| Carvalho, Gil B; Kapahi, Pankaj; Benzer, Seymour (2005) Compensatory ingestion upon dietary restriction in Drosophila melanogaster. Nat Methods 2:813-5 |
| Kapahi, Pankaj; Zid, Brian M; Harper, Tony et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885-90 |
| Wang, Horng-Dar; Kazemi-Esfarjani, Parsa; Benzer, Seymour (2004) Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Natl Acad Sci U S A 101:12610-5 |
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