Diet and the determination of longevity in Drosophila melanogaster

Caloric restriction (CR) is an important tool for the study of aging. Recent advances have shown a substantial genetic component of the response to CR, necessitating an expansion of available knowledge about the effects of CR on favored model organisms such as Drosophila melanogaster for the study of genetics. The experiments and results described in this thesis indicate that CR produces lifespan extension in Drosophila that is similar to that reported for rodents. Furthermore, there are observable changes of body weight, body composition, and activity levels in response to diet for Drosophila that parallel similar findings in other organisms. ^ A substantial advantage to studying CR in Drosophila is the relative ease with which large populations can be used in the application of a biodemographic description for the response to CR. Age-specific mortality data shows that increased longevity as a response to decreased dietary calories in Drosophila occurs through a slowing of the rate of aging. Most importantly, diet can affect the rate of aging throughout the Drosophila lifespan, and institution of CR even at late ages produces a substantial prolongation of longevity. However, application of CR in mid- to late-life cannot fully reverse the aging process, and there is residual detriment to lifespan as a result of initially normal- or high-caloric diets. ^ This text also details an investigation of sex differences and the influence of reproduction on the relationship between CR and longevity in Drosophila. Studies of virgin fly populations and various diets designed to manipulate fertility indicate that the close relationship between fertility and longevity in Drosophila can be dissociated and that the primary effects of diet on lifespan do not occur as a result of modulations in fertility. Also, there is notable divergence in the response of the different sexes to CR beyond what has been previously reported, with an observed rebound in male longevity at very high caloric levels. These findings substantially advance our understanding of the relationship between diet and longevity in Drosophila, and will be of great use to investigators seeking to apply CR in Drosophila as a means for studying the progression of aging.