Genes and Pathways that Modulate Neural Decline with Age

2009 senior Scholar Award in aging

A long-standing aspect of aging is that the brain, with age, undergoes cognitive decline and perhaps degeneration. Such decline may not only underlie normal loss of brain function with age, but also contribute to or advance diseases of the nervous system, such as Alzheimer's disease, Parkinson's disease and others. Despite the importance of this issue, there are few experimental systems in which age-dependent neural decline can be experimentally approached in order to characterize in detail this aspect of the nervous system, and, importantly, define ways by which to interfere with decline of the aging brain. Defining such pathways may lead to treatments that promote cognitive function with age, as well as improve neurological diseases where age is a prominent risk factor, like Alzheimer's disease and others.

Drosophila, the fruit fly, is an outstanding and powerful simple system that has allowed many neurological processes relevant to humans to be studied. Our past work has been focused on using the fly to reveal insight into human neurodegenerative diseases. We now propose to develop the fly as a system in which to study the processes of normal neurological decline with age. Select neural systems in the fly present an opportunity to observe naturally occurring age-dependent decline of the brain, akin to our cognitive decline with age. In the fly, we will characterize these processes in order to reveal genes and drugs that modulate neural decline. Our studies will thus use the power of a simple and highly manipulable genetic system in order to provide the foundation for new approaches to enhance age-dependent function of the brain.