Longevity is controlled by a combination of genetic and environmental factors. The search for genes that regulate longevity greatly benefit from invertebrate model organisms. However, identifying longevity genes in vertebrates has been hampered by the absence of short-lived vertebrate models. The exceptionally short-lived fish species Nothobranchius furzeri (N. furzeri) represents an extremely promising new vertebrate model for aging. Remarkably, N. furzeri comprises several natural populations that differ in life expectancy. This difference in lifespan is likely due to genetic factors as it persists even after several generations in captivity. However, genetic or genomic tools for this species of fish are not available yet. The goal of this grant proposal is to examine the genetic inheritance of longevity and age-related traits, and to generate a genome-wide microsatellite linkage map of N. furzeri. To achieve these goals, we propose the following experiments: 1. To characterize aging and age-related traits in the short-lived and long-lived populations of N. furzeri 2. To analyze the genetic pattern of inheritance of the longevity trait in N. furzeri 3. To generate a linkage map for the short-lived fish species N. furzeri. A combination of genetics and molecular approaches will be used to develop these aims. The generation of a genetic linkage map in this extremely short-lived vertebrate will be helpful for the scientific community, as it will allow the mapping of traits that differ between natural populations of fish in these species, including aging and cognitive behaviors. As aging pathways tend to be conserved, mapping aging traits in this short- lived vertebrate is likely to have important implications for longevity in other species. Public Health Relevance: The proposed project is aimed at developing genetic tools to identify the genes underlying aging and longevity in a new vertebrate model for aging, the extremely short-lived fish Nothobranchius furzeri. As a number of human diseases, including cancer, diabetes, and neurodegenerative disorders, have an age-dependent component, understanding the molecular bases of aging may provide new avenues to prevent and treat these age-dependent diseases.
| Valenzano, Dario Riccardo; Kirschner, Jeanette; Kamber, Roarke A et al. (2009) Mapping loci associated with tail color and sex determination in the short-lived fish Nothobranchius furzeri. Genetics 183:1385-95 |
