Wolfgang Maier, Martin Regenass, Monique Thomas and Joy Alcedo. Aging is influenced by several factors, which include the environment of the animal. For example, mutations that impair sensory function extend the lifespan of C. elegans, which suggests that lifespan, of at least this animal, is regulated by the perception of environmental cues (1). Specific sensory neurons appear to regulate lifespan, at least in part, through the insulin/IGF-1 pathway (1, 2). Since several putative insulin-like ligands are also expressed in these neurons (3), it is possible that an environmental signal(s) sensed by these neurons regulates the production of these ligands. To elucidate further the molecular mechanisms of the sensory influence on lifespan, we are carrying out an RNA-mediated interference screen for enhancers and suppressors of the lifespan phenotype of sensory mutant animals. As we identify genes involved in the sensory influence on lifespan, we will study their expression patterns using GFP-fusion reporter constructs to determine in which cells they function. We also plan to measure the lifespans of strains in which the particular gene was knocked out or overexpressed. Furthermore, we will conduct pertinent studies on how the gene products function, such as testing if the functions of these genes require each other or involve the
daf-2 insulin/IGF-1 pathway or other signaling pathways in the worm known to influence its lifespan. References: (1) Apfeld, J., and C. Kenyon. 1999. Nature (Lond.). 402: 804 809; (2) Alcedo, J., and C. Kenyon. 2004. Neuron 41: 45 55; (3) Pierce, S. B., et al. 2001. Genes Dev. 15: 672 - 686.