(From the application): Aging and neurodegenerative disease inflict great suffering and financial cost on individuals and society. Although these processes are poorly understood, recent advances including genetic analysis in small organisms such as C. elegans and D. melanogaster, the identification of human disease genes, the construction of models by genetic manipulation in mice and developments in cell biology have opened up new and highly fruitful entry points for molecular analysis. For example, the process of aging has long been considered passive in nature; however, studies in C. elegans demonstrate the hormonal regulation of aging by genes with human homologs. Telomere loss causes cell senescence in vitro, and gene knock-out studies suggest that telomere loss in vivo may contribute to tissue decline. The study of prions has led to a new paradigm for neurodegenerative disease involving changes in protein conformation. Human genetics has identified proteins that participate in the pathogenesis of Alzheimer's and Parkinson's diseases. In general, many previously mysterious disorders are now known to have a specific molecular basis that can be analyzed using genetic, cellular and molecular approaches. These apparently intractable problems have become ripe for analysis, and extremely talented young investigators are now showing an increased interest in them. Demographic shifts towards an aging population increase the magnitude of the social problem and make the training of first-rate researchers all the more urgent. As a center of excellence committed to the training of students and postdoctoral fellows as well as the study of aging and neurodegenerative disease, UCSF is in a unique position to help solve these major biomedical problems. Here we propose to create a training program that takes advantage of UCSF's commitment to aging and neurodegenerative disease and interactive environment. The program will facilitate training and collaborations and focus the interests of students and faculty on aging and neurodegenerative disorders, with the goal of spawning new research initiatives that will lead to better understanding and more effective intervention.
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