Physical activity (PA) has numerous and profound benefits on health and function, yet there is limited knowledge of the mechanistic signals that underlie these benefits. Such knowledge is critical for optimizing the effective use of PA as a preventive or therapeutic intervention strategy for specific diseases and in specific populations. The overarching goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to address this knowledge gap by characterizing the molecular responses to PA. This will be accomplished through the collection of blood and tissue samples from both humans and animals, which will then be subjected to extensive ?Omics? analyses. By generating a comprehensive map of molecular responses to PA, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. The University of Colorado Anschutz Medical Campus (CU-AMC) is exceptionally well poised to lead a MoTrPAC Adult Clinical Center and to contribute to all Consortium activities. Our investigators and collaborators have extensive experience with complex clinical PA intervention trials, including tissue sampling, in cohorts spanning the entire adult age spectrum. Our expertise extends across multiple physiological systems, diseases, and health conditions, and includes broad proficiency in physiologic, metabolic, and morphometric phenotyping. The facilities at CU-AMC for MoTrPAC activities are outstanding. The proposed MoTrPAC ? Colorado Clinical Center will accomplish the following Specific Aims (SA): SA1: Contribute to, and lead when appropriate, all MoTrPAC Phase 1 planning activities (Year 1) described in RFA-RM-15-015 through participation on the MoTrPAC Steering Committee and Subcomittees. The local goals for Phase 1 will be to accomplish tasks (e.g., obtain regulatory approvals, train staff) that will enable Phase 2 to start at the beginning of Year 2. SA2: Recruit and enroll 450 adults at CU-AMC (or the number determined during Phase 1), conduct the acute PA tests and PA intervention according to protocols established by the Consortium, and carry out all other MoTrPAC Phase 2 activities (Years 2 to 5). Highly accomplished clinical investigators will lead the seven ?teams? that will be responsible for: recruitment, screening, and retention; physiologic, metabolic, and morphometric phenotyping; biospecimen acquisition; biospecimen processing; acute PA tests; chronic PA interventions; and data management and quality assurance. SA3: As animal and human data become available from the Chemical Analysis Sites and Bioinformatics Center, we will participate in all Phase 3 activities, including data analysis, preparation of manuscripts, and dissemination of results. These activities will be guided by the MoTrPAC Steering Committee and Subcommittees. On the local level, we will host an annual 1-day local symposium on PA, Health, and Fitness to catalyze the interest of investigators at CU-AMC and other nearby academic institutions in MoTrPAC.