Exploration of the C.elegans insulin-like aging pathway

1998 senior Scholar Award in aging

Dr. Ruvkun has previously shown that an insulin-like signaling pathway regulates longevity and metabolism in C. elegans. The most important output of this pathway in C. elegans is the transcription factor DAF-16. Dr. Ruvkun now proposes to search for the downstream targets of DAF-16 in order to identify the downstream daf-16 genes involved in longevity control.
Gary Ruvkun Ph.D.
Harvard Medical School

Dr. Ruvkun has shown that insulin-like pathways regulate longevity and metabolism in C. elegans. His genetic analysis indicates that the keys to longevity in C. elegans insulin-like signaling are the targets of the transcriptional factor DAF-16, a factor that has human homologues. Additionally, Dr. Ruvkun performed what he described as the first reported comprehensive functional genomic screen for longevity genes. By screening 5,690 C. elegans genes using RNA interference (RNAi), he found that genes important for mitochondrial function appeared critical for determining C. elegans lifespan. A concurrent classical genetic screen also identified a mutation affecting mitochondrial function that increased lifespan. The animals with impaired mitochondrial function and extended lifespan had reduced ATP content and oxygen consumption rates, which indicate altered metabolism. This suggests that there is a complex relationship between metabolism and longevity.