The genetic determinants of longevity in C. elegans CALS Impact Statement uri icon

abstract

  • We use the nematode C. elegans as a model system to investigate how longevity of an organism might be regulated at the molecular level. Our research focuses on elucidating the mechanism whereby insulin signaling affects lifespan in C. elegans, and using a functional genomics approach to globally identify and characterize the genetic determinants important to the C. elegans lifespan. Insulin signaling plays a critical role in metabolism, development, and longevity in diverse species, from nematodes to mammals. We have combined comparative genomics with biochemical and functional assays in C. elegans to identify evolutionarily conserved genes that might be downstream effectors of insulin signaling. We hope the continued characterization of these putative downstream genes will help to elucidate how insulin signaling mediates its diverse biological outputs. We have also used genome-wide RNA-interference screens to comprehensively identify new genes that affect C. elegans longevity. We are currently using genetic and molecular approaches to classify each of these candidate longevity genes into specific pathways. We hope that further functional characterization of these candidate longevity genes will provide a global view of the diverse pathways that might affect organismal lifespan.