ISC Summary/Abstract: The fundamental concepts underlying the Integrative Systems Core (ISC) are that age-related alterations in mobility and balance develop subtly, prior to overt clinical problems, and are due to multi-system interacting changes. The ISC provides state-of-the-art multidisciplinary expertise on age-related change in mobility via collaborating laboratories encompassing 1) whole-body movement and balance, 2) nervous system structure, function and energetics, and 3) cardiopulmonary and musculoskeletal structure, function and energetics. These laboratories collaborate with each other, as well as with other Pepper Cores and Centers to bring simultaneous multisystem evaluation to research studies. During the current cycle, the ISC supported 11 pilot exploratory studies (PES), 2 developmental projects (DPs), 23 REC trainees (7 scholars), and over 50 externally funded projects (EP), virtually all of which involved collaboration with other Pepper Cores, other Pitt Centers, other Pepper Centers, and other institutions. In this renewal, the ISC will support 3 PES and 2 DPs in collaboration with other Pepper Cores. The ISC will add extensive and innovative new resources for: 1) non-invasive in-vivo assessment of mitochondrial function in heart, brain and muscle; 2) cardio-pulmonary physiological changes during exercise; 3) muscle structure, innervation and energetics including spinal cord physiology; 4) a validated set of tasks for detailed assessment of dual tasks and the cognitive-motor interface; and 5) wearable devices to measure cerebral and muscle activity while walking (NIRS and high-density EMG), as well as in-place spatial navigation via combined accelerometry-GPS systems outside the laboratory. Our specific aims are: 1. Provide cutting-edge resources and expertise to concurrently study both whole-body as well as multiple systems and physiologic mechanisms affecting mobility and balance during aging, both during study planning as well as during implementation and analysis. 2. Develop and test novel techniques and approaches to address gaps and needs for multi-system evaluation of mobility and balance. 3. Support the training mission of the OAIC by educating and supporting the work of Pepper trainees through workgroups, seminars, “field trips” and active involvement in trainee research projects. 4. Collaborate with other Cores and Centers in and outside Pitt on OAIC-related activities. 5. Continuously monitor, evaluate and communicate about Core activities both within and among Core laboratory leaders, as well as with other Pepper Cores, Pepper leadership and NIA. In summary, the ISC has formed the heart of the Pittsburgh Pepper since its inception and has been instrumental in creating and disseminating new knowledge and new approaches to prevent and treat age- related problems with mobility and balance.