Genetic analysis of immunosenescence in Caenorhabditis elegans

2008 new Scholar Award in aging

The age-associated decline in immune function with advancing age, termed immunosenescence, has been well documented in humans, but the underlying mechanisms remain poorly understood. Indeed, the decline in immune function itself may contribute to the aging process. We propose to identify and characterize the genes governing the age-related decline in the immune system of the roundworm, Caenorhabditis elegans.

A community of scientists that study the genetics of the worm has developed over the past 40 years, drawn to the simple anatomy and life cycle of the worm, and the ease with which genes can be studied in the worm. Many human genes have ancient relatives that function in the worm, and insights gained from the study of worms often have had implications for our understanding of human development and disease. Indeed, studies of aging in the worm have provided basic insights into the genetic control of longevity. Our laboratory has been focused on the study of immunity in the worm, with the anticipation that the study of worm immunity will reveal basic insights into mechanisms of immunity functioning in evolutionarily diverse species.

We propose to define how the aging process affects immunity in the worm, including the study of how genetic changes that influence longevity affect immune function. We will take advantage of the experimental tractability of the worm and identify and characterize the genes that are required for immunity in aging worms. We will also define how the activity of genes required for immunity changes during the aging process. We anticipate that these studies will provide molecular genetic insights into how age-related changes in the evolutionarily ancient immune system of the worm contributes to immunosenescence, with implications for our understanding of this phenomenon in humans.