Over the past 16 years, the Wake Forest University Claude D. Pepper Older Americans Independence Center (WFU OAIC) has excelled in its mission to assess risk factors for physical disability in older adults, develop and test effective prevention therapies, and train new leaders in research on aging and disability. In this competetive renewal, we propose to utilize the new findings and subsequent hypotheses generated during this cycle to extend our current skeletal muscle-based disability model to integrate adipose tissue mass and distribution into multiple disability-related pathways according to the theme: Integrating pathways affecting physical function for new approaches to disability prevention. The WFU OAlC's 5-year goal is to provide the scientific expertise, leadership, and resources to define and formulate evidence-based responses to the consequences of increased adiposity, both at the whole body and compartmental levels. Progress will be optimized by refining a disability model which integrates muscle, adipose, cognitive-behavioral factors, and common co-morbidities, and is supported by bi-directional translational and mechanistic research. To achieve this goal the WFU OAIC will integrate the work of seven Cores lead by experienced senior investigators: the Leadership and Administrative Core, the Research Career Development Core, the Pilot / Exploratory Studies Core, the Clinical Research Core, the Molecular Sciences Resource Core, the Biostatistics and Data Management Core, and the Biolmaging Resource Core. Together these cores will provide the infrastructure and services needed to support and effectively coordinate the efforts of investigators, junior faculty, and innovative research projects. During the first year, the OAIC will train 5 junior faculty and support 12 externally-funded studies (8 stemming directly from prior OAIC work), 3 research development projects and 4 pilot studies. In addition, the WFU OAIC proposes to continue coordinating the overall national OIAC program via its Coordinating Center Core expanding its scope to: 1) lay the foundation for an OAlC-based research network, and 2) increase coordination of junior faculty development programs across multiple organizations charged with aging-research leadership development. In the 2002-2007 cycle, the WFU OAIC supported 17 external studies, 14 pilot studies, supported, 12 junior faculty members and contributed to 403 research publications. Particular strengths of the WFU OAIC are its highly integrated cores, projects, and investigators all focused on a common, strategically important research theme, and its multi-disciplinary, collaborative, nurturing environment for developing research and leadership skills in junior investigators, and an exceptionally high level of institutional support including substantial new investments in aging-research.