Project Summary/Abstract: This application is for the formation of an Adult Clinical Center in response to RFA-RM-15-015 “Molecular Transducers of Physical Activity Clinical Centers (U01)” (MoTrPAC). Physical activity is an important lifestyle behavior that has been shown to be associated with morbidity and mortality from numerous chronic diseases. This has led to current public health recommendations of 150 min/wk of moderate-intensity physical activity or 75 min/wk of vigorous physical activity to achieve significant health- related benefits, and for recommendations to engage in resistance exercise. Despite the abundance of data to support physical activity as a key lifestyle factor that can prevent, delay, or reverse the onset of a variety of health-related conditions, the specific underlying physiological mechanisms and pathways by which this occurs are not fully established. Our team of investigators is well-positioned to be an Adult Clinical Center and achieve the goals and objectives outlined in this RFA. We have the capacity in Pittsburgh to recruit, retain, train, and assess the 450 participants that are required at each Adult Clinical Center. We will recruit 450 participants at the Pittsburgh Adult Clinical Center, which will include untrained subjects who will be randomized to the intervention (72% of the sample, N=324) or control condition (12% of the sample, N=54) and trained subjects (16% of the sample, N=72). Untrained participants will be randomized to one of the following for a period of 12 weeks: 1) Control (UN- CON) that will maintain their current level of physical activity; 2) Moderate-Intensity Physical Activity (UN-MOD) that will progress to 150 min/wk of supervised moderate-intensity endurance physical activity; 3) Vigorous- Intensity Physical Activity (UN-VIG) that will progress to 75 min/wk of supervised vigorous-intensity endurance physical activity; 4) Resistance Training (UN-RES) that will engage in supervised resistance exercise. In addition, exercise trained participants (50% endurance trained, 50% resistance trained) will be recruited and will undergo baseline testing only. Thus, we propose to form an Adult Clinical Center at the University of Pittsburgh to achieve the following objectives of MoTrPAC: 1. To recruit, retain, and collect data on 450 participants (378 untrained and 72 trained) at the Pittsburgh site that will contribute to the 2,700 total participants across the Adult Clinical Centers. 2. To demonstrate the effectiveness of our training program, we will compare changes in cardiorespiratory fitness in untrained participants randomized to 12-weeks of moderate-intensity endurance exercise training (UN-MOD), vigorous-intensity endurance exercise training (UN-VIG), resistance training (UN-RES) or control (UN-CON). 3. To demonstrate the effectiveness of our training program, we will compare changes in musculoskeletal fitness in untrained participants randomized to 12-weeks of UN-MOD, UN-VIG, UN-RES...