Characterization of natural genetic variation underlying age-specific changes in immunity using Drosophila melanogaster.

摘要

Senescence is reflected in the age-related functional decline of many physiological traits. One trait that shows age-related decline across a broad range of organisms is the immune response. While extensive work on mammalian systems has revealed the cellular and physiological hallmarks of age-related declines in immunity, we currently know very little about the genetic basis of this decline. Earlier work in our lab, using Drosophila lines derived from a natural population, has demonstrated genetic variation in the age-specific immune function. The major goals of this project were to confirm the effect of age on the variation in immune function, characterize genetic variation in age-specific immune response, explore the extent to which the transcriptional response to infection plays in clearing an infection and identify candidate genes that contribute to the natural variation in age-associated changes in the innate immune response. Next, functional characterization experiments were conducted on three candidates genes that were found to associate with variation in immune response at 4 weeks of age. Lastly, gene co-expression networks were used as an alternative approach for identifying genes involved in age-associated changes in the innate immune response. This work has provided novel candidate genes involved in the age-related changes in immune function as well as genes that explain age-specific variation in immune function.