Dissecting the Processes of Aging Using the Nematode Caenorhabditis elegans

This chapter explains the process of aging using the nematode Caenorhabditis elegans. Molecular genetic analysis of aging in C. elegans begins with the startling discovery of the first gerontogene. C. elegans contains a large family of insulin-like sequences. The genes are frequently found in clusters and are derived likely from recent duplication events. The gene family shares roughly 25 to 40 percent amino acid identity, yet they all contain signatures of insulin-like molecules. Soil is the natural habitat of the free-living nematode C. elegans and when a food source is exhausted, or in response to other adverse conditions, an alternative developmental program called the dauer pathway is activated. The decision to suspend reproductive development and instead become a long-lived, growth-arrested dauer is made at the first larval stage (L1). Adverse conditions are sensed by chemosensory and thermosensitive mechanisms, whereas overcrowding is detected by the local concentration of a lipid soluble pheromone secreted by L1 animals. Modulating DAF-16 transcriptional activity is a major function of insulin signaling in C. elegans, and nuclear localized DAF-16 plays a necessary role in increased longevity.