An Exploration of the Genetics and Molecular Mechanisms Underlying Conserved Longevity Interventions

Aging is a degenerative process that causes a time-dependent deterioration of virtually every biological system in the majority of species. Age is the primary risk factor for many human diseases, including the top causes of death modern societies. Developing treatments to slow the aging process has the potential increase human life span and simultaneously prevent or improve outcomes in countless diseases. Studying aging in mammals is challenging due to the relatively high longevity of most mammalian species and the costs associated with maintaining populations of mammals in the laboratory for their entire life span. The invertebrate organisms Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster have emerged as central models in aging due to relatively short life spans, ease of maintenance in the laboratory, well characterized genetics, and the availability of a wide range of genetic and biochemical tools. By focusing on genetic pathways and interventions that influence longevity in a similar manner across these evolutionarily divergent species, we can gain insight into the biology of aging in mammals. The application of genome-scale techniques in aging research has started to define the range of genetic and environmental factors involved in longevity determination, and the high degree of intercommunication between these factors. This dissertation reviews current progress toward identifying and understanding conserved longevity interventions and presents several current lines of investigation aimed both at developing tools for analyzing the complex interactions between aging factors and at probing the mechanism of action of specific longevity interventions.