PROJECT SUMMARY Population projections made by the US Census Bureau indicate that ~20% of the population will be >65 years old by 2030, and if correct, this demographic change will have a major impact on the economy and health of our nation. However, the mechanisms underlying normal and pathological human aging are still poorly understood, especially those associated with the nervous system, and safe and effective therapies have yet to be developed. Therefore, the primary aim of this T32 program is to provide students with basic, translational, and clinical research training in the Neuroscience of Aging and Neurodegeneration. Based on the experience of our 20-member faculty, who have previous trained 60 pre-doctoral students and 120 postdoctoral fellows, we expected that a total of 12 PhD or PhD/MD students and 8 postdoctoral fellows will be trained during the proposed 5-year funding period. Our program is thus expected to make a significant contribution to a national effort ensuring that there will be a sufficient number of trained researchers available in the ensuing decades, with expertise in normal and pathological human aging. Importantly, our program does not duplicate any other training program at OHSU, and it is the only mechanism by which students can obtain comprehensive research training in the Neuroscience of Aging and Neurodegeneration in the Pacific Northwest. The T32 training faculty bring ~$20,000,000 in direct research funds to the Oregon Health and Science University (OHSU) each year, in support of basic, translational, and clinical aging/neurodegeneration research. Furthermore, the faculty have primary appointments within the Schools of Medicine and Engineering, the Layton Aging & Alzheimer's Disease Center, the Oregon Institute of Occupational Health Sciences (OIOHS), the Vollum Institute, the Advanced Imaging Research Center (AIRC), the Jungers Center for Neuroscience Research, and the Oregon National Primate Research Center (ONPRC). Thus, our program offers training using a broad spectrum of animal models, including invertebrates, rodents, and nonhuman primates, as well as humans. It also provides extensive Research Core support and access to a wide range of cutting-edge resources and methodologies, including advanced in vivo brain imaging at one end of the spectrum and RNA- seq gene expression profiling at the other. Currently, the program's main aging-related research focus areas include: perturbed circadian rhythms, neuroendocrine-associated disorders, cognitive decline, movement disorders, and neurodegenerative diseases such as Alzheimer's and Parkinson's. A special emphasis of our program is for the trainees to conduct their research projects within a ?bench-to-bedside? framework, ensuring that even our basic science trainees will obtain first-hand exposure to translational or clinical aging research. The breadth of the training will be further enhanced by requiring all of our trainees to attend a comprehensive 3-term Neuroscience of Aging graduate training course, as well as a monthly Neuroscience of Aging journal club and a monthly Responsible Conduct in Research class, and participate in OHSU science outreach efforts.