Caloric restriction (CR), a decrease in nutritional level without causing malnutrition, is well known to increase lifespan across species, from yeast to rodents. Ad libitum feeding can therefore be viewed as having a toxic effect on lifespan. Indeed, overnutrition in humans is one of the leading risk factors for age-related diseases and mortality. We propose to characterize the effects of overnutrition in Drosophila, and seek ways to mitigate them by finding mutants that show either enhanced sensitivity or resistance to overnutrition. The identification of molecular pathways involved should provide tools in the understanding of this phenomenon, by leading us to the downstream genes that manifest the lifespan changes. Examination of the pathological and physiological changes resulting from overnutrition in normal and mutant flies will cast light on their involvement in aging and age-related diseases. Most investigations have been directed at the effects of undernutrition as a beneficial factor in extending lifespan. This proposal represents an alternate approach, focusing on overnutrition to exaggerate deleterious effects, thus providing a sensitized system in which to discover methods of ameliorating them.
| Cho, Jaehyoung; Hur, Jae H; Graniel, Jacqueline et al. (2012) Expression of yeast NDI1 rescues a Drosophila complex I assembly defect. PLoS One 7:e50644 |
| Al-Anzi, Bader; Armand, Elena; Nagamei, Paul et al. (2010) The leucokinin pathway and its neurons regulate meal size in Drosophila. Curr Biol 20:969-78 |
| 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; 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 |
