Effective pilot and exploratory studies (PES) provide critical preliminary data to support successful research proposals, particularly for early-career investigators who also need guidance in designing research studies and writing study proposals. The Wake Forest OAIC Pilot and Exploratory Studies Core (PESC) has been highly effective, managing a robust portfolio of PES aligned with the WF OAIC theme, ranging from basic science studies examining biomolecular pathways to the development and testing of innovative approaches to characterize and improve physical function. During the current cycle, PESC has been extremely productive, leading to 19 external grant awards totaling $18.9 million and 115 PESC-related publications. In the next cycle, the PESC proposes will continue our highly successful, coordinated, multi-faceted group efforts to promote PES; implement new innovations to promote multidisciplinary research, and further refine processes. The overall PESC goal is to enable investigators to develop key information needed for the design of definitive, externally funded, translational research studies that promote the WF OAIC mission to understand pathways influencing physical function and to develop new approaches to disability prevention and treatment. This will be achieved by executing the following Specific Aims: 1) Identify and promote promising areas of aging research; 2) Identify and recruit talented early-career and selected other investigators from aging and complementary fields to focus on OAIC-themed research, in concert with the Research Education Component (REC); 3) Solicit and facilitate competitive research proposals, provide constructive feedback, and conduct expert peer review to select proposals with the best science and career development opportunities, 4) Coach and mentor investigator teams to maximize the success and impact of research projects; 5) Team with other WF OAIC cores to facilitate successful completion of the selected pilot projects and mentor early-career investigators to advance their development as successful translational scientists; and 6) Continuously evaluate, refine, and optimize OAIC PESC processes and procedures. Under the continuing leadership of Drs. Kitzman and Register, the PESC will support 4 innovative pilot projects in the first year, all led by talented early- and mid-career investigators, including REC Scholars and investigators new to aging. They extensively use OAIC cores and represent the full range of translational science to address physical function and disability in older persons. These include: testing feasibility of a novel home-based exercise program in older rural cardiac rehab patients; assessing relationships between vision, brain networks, and physical function; examining the effects of metformin on mitochondrial function and physical performance; and exploring relationships between circulating muscle-specific exosomes and physical function. All projects align with the OAIC mission...