PgmNr D1162: The Loss of Regenerative Potential in the Aging Drosophila Germline Stem Cell.

Authors:
R. E. Kreipke; H. Ruohola-Baker


Institutes
University of Washington, Seattle, WA.


Keyword: regeneration

Abstract:

Aging is a complex biological process, comprised of a large number of both cellular and organismal changes that, together, lead to the progressive decline in tissue and organ function. In addition to declining function in somatic cells, aging tissues are also marked by a decrease in the proliferative capacity of pluripotent cells, hampering their regenerative capacity and ability to respond properly to injury and insult. However, the mechanisms that govern the regenerative competence of aging stem cells still remain unclear. The Drosophila melanogaster germline stem cell (GSC) niche offers a powerful model with which to study developmentally regulated changes in stem cell regeneration and their response to insult. In the young fly, GSCs are resistant to the apoptotic effects of ionizing radiation. Dying daughter cells release a protective signal that inhibits the apoptotic machinery in germline stem cells, prompting them to become quiescent rather than apoptotic. The GSCs are able to later re-enter the cell cycle and repopulate the daughter cells. This protective mechanism highlights a key difference between the proliferative capacities of somatic and germline cells. To date, though, the ability of the aged ovary GSC has not been probed. We compared the ability of 2-, 4-, and 6-week old germline stem cells to regenerate daughter cells following exposure to ionizing radiation. We found that, while aged GSCs were able to survive exposure to ionizing radiation, their ability to exit quiescence and re-enter the cell cycle to repopulate the germaria were compromised when compared to young GSCs. This suggests that the mechanisms that preserve the regenerative capacity of GSCs may degrade with age. To identify novel regulators of GSC regeneration, we used newly developed techniques of protein knockdown to disrupt protein function. This will allow us to screen for genes that regulate GSC regeneration following exposure to ionizing radiation and begin to identify genes that contribute to age-related decline in GSC proliferation.