In the nematode Caenorhabditis elegans starvation or overcrowded conditions may activate a developmental switch so that the dauer larvae, a developmental arrested, non- feeding animal, is produced. Past investigations have identified both dauer- constitutive mutations, which cause animals to form dauer larvae in the presence of abundant food, and dauer-defective mutations, which prevent dauer formation under normal inducing conditions. Recently, temperature-sensitive dauer-constitutive alleles of the gene daf-2 have been shown to prolong adult lifespan (and be prevented by dauer-defective mutations in the gene daf-16). Additionally, mutations in daf-12 and daf-23 also affect this process. The goal of the present proposal is to understand how specific daf genes affect life span and to use these genes to understand the molecular and physiological processes that underlie life span determination. Emphasis will be placed on the analysis of the daf-2 and daf-12 genes. The complete sequences and patterns of expressions of both genes will be determined with particular emphasis in the latter experiments to ascertain whether specific cells are important for life-span determination. Downstream targets or genes interacting with or regulated by these genes will also be sought.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Mccormick, Anna M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Missouri-Columbia
Schools of Arts and Sciences
United States
Zip Code
Chen, Di; Zhang, Jiuli; Minnerly, Justin et al. (2014) daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan. PLoS Genet 10:e1004699
Park, Donha; Jones, Karen L; Lee, Hyojin et al. (2012) Repression of a potassium channel by nuclear hormone receptor and TGF-? signaling modulates insulin signaling in Caenorhabditis elegans. PLoS Genet 8:e1002519
Park, Donha; O'Doherty, Inish; Somvanshi, Rishi K et al. (2012) Interaction of structure-specific and promiscuous G-protein-coupled receptors mediates small-molecule signaling in Caenorhabditis elegans. Proc Natl Acad Sci U S A 109:9917-22
Ruzanov, Peter; Riddle, Donald L; Marra, Marco A et al. (2007) Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults. Exp Gerontol 42:825-39
Ruzanov, Peter; Jones, Steven J; Riddle, Donald L (2007) Discovery of novel alternatively spliced C. elegans transcripts by computational analysis of SAGE data. BMC Genomics 8:447
Holt, Suzan J (2006) Staying alive in adversity: transcriptome dynamics in the stress-resistant dauer larva. Funct Integr Genomics 6:285-99
Jensen, Victor L; Gallo, Marco; Riddle, Donald L (2006) Targets of DAF-16 involved in Caenorhabditis elegans adult longevity and dauer formation. Exp Gerontol 41:922-7
Halaschek-Wiener, Julius; Khattra, Jaswinder S; McKay, Sheldon et al. (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15:603-15
Jia, Kailiang; Chen, Di; Riddle, Donald L (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131:3897-906
Holt, Suzan J; Riddle, Donald L (2003) SAGE surveys C. elegans carbohydrate metabolism: evidence for an anaerobic shift in the long-lived dauer larva. Mech Ageing Dev 124:779-800

Showing the most recent 10 out of 21 publications