Understanding variation in aging within human populations requires that we merge insights gained from functional analyses within model systems with an understanding of the historical forces that structure variation within natural populations. The model nematode, Caenorhabditis elegans, has served as one of the most powerful systems for uncovering the genetic basis of conserved pathways with large effects on longevity and stress resistance. However, recent evidence from natural isolates of C. elegans suggests that this nematode will serve as a poor model for studying variation in aging within natural populations. In this small grant research program application, we propose to build upon the strength of the C. elegans model system for understanding the genetics of aging by developing the closely related nematode, C. remanei, as a model system for understanding how these genetic systems behave in a natural system. Extensive preliminary work on molecular genetic variation within C. remanei populations, as well as quantitative genetic analyses of variation in longevity within and between these populations, demonstrates that C. remanei should provide a powerful platform for understanding the accumulation of variation in aging within natural populations.
We aim to: 1. Measure variation in longevity and stress resistance within and between natural populations of C. remanei. The usefulness of C. remanei to serve as a model for natural variation in aging processes depends on the amount actual variation in age-related processes within these populations. Preliminary data suggests that there can be substantial differences among strains within this species. Such variation can serve as the basis for future studies of the complex genetics that surely must characterize individual differences in aging in most populations, including humans. 2. Measure the sequence variation within the insulin signaling pathway known to have a large influence on aging and extended life spans within C. elegans. Several genes with large effects on aging within C. elegans have been well characterized, and many of them participate in an insulin-like signal transduction pathway that regulates the dauer (resting) stage of C. elegans. These genes are likely candidates for individual differences in longevity. Further, studying the molecular population genetics of these loci will yield insights into how evolutionary processes shape an important pathway that is now thought to have a conserved influence on aging across all animals. Work conducted under this project will therefore serve as a springboard for future work on the complex genetics of aging, as well as providing valuable resources for those working with nematode model systems. ? ? ? ?
