Cell Fate Decisions and Differentiation in the Aging Drosophila Intestine
2013 new Scholar Award in aging
Aging is characterized by a progressive functional decline in many organs. Understanding the changes that cause this decline and identifying therapeutic manipulations that can delay or revert these deleterious effects of age are some of the fundamental goals of aging research. The long term functionality and integrity of many organs depends critically on the function of resident stem cell populations. However, the mechanisms that control the function of these stem cells erode in older individuals. In particular, in young tissues, stem cells typically give rise to multiple types of cells and carefully control the proportion of each of these cell types to maintain healthy tissues. With age, this control is lost, creating an imbalance in the numbers of cells that compose older organs and leading to impaired function. Interestingly, similar mechanisms are thought to contribute to cancer formation and progression and, in some case, to degenerative diseases. Importantly, while this phenomenon has been described in many organs and different species, the mechanisms that drive this age-related decline in the control of stem cells remain poorly understood. The proposed project is designed to identify some of the changes that cause these age-related defects. We will use the fruitfly Drosophila melanogaster as an experimental model, as this tractable organism experiences age-related changes of their stem cells that are similar to the ones observed in mammals. We will perform experiments that will investigate the role of a newly identified signaling pathway in the aging fly intestine. In addition, we will test whether stress and bacterial infection affect this process and contributes to gut aging. Finally, we will try to identify genetic or therapeutic manipulations that are capable of preventing this decay and ask whether such interventions extend healthy life and promote longevity. Drosophila research has a long history of important discoveries in the biomedical field, leading to significant applications in higher organisms, including humans. Hence, it is expected that the results of our studies will provide new insight into mechanisms that are likely to contribute to normal aging as well as diseases, such as degenerative syndromes, and cancer.