ABSTRACT The risk factors that contribute to cardiovascular disease originate in childhood and adolescence, track into adulthood, and have deleterious effects on long-term biopsychosocial health. Phenotypic sleep and fitness are strongly associated with mechanisms involved in the development and progression of cardiovascular disease and its risk factors (e.g., elevated body-mass index, adiposity, metabolic syndrome, elevated serum lipids, elevated blood pressure, inflammation, autonomic nervous system imbalance, poor nutrition and diet, and physical inactivity). Sleep and fitness are essential interacting physiological functions that are associated with robust metabolic, hormonal, and cognitive responses, as well as with genomic and metabolomic adaptive mechanisms. Both insufficient sleep and poor fitness are at epidemic proportions in youth and are associated with acute health threats and increased disease risk across the lifespan. However, little is known about the underlying mechanistic pathways that govern the interactions between fitness and sleep in developing youth in their modulation of cardiovascular disease risk. This proposed study aims to fill a crucial gap in the understanding how sleep and fitness interact to impact cardiovascular disease risk factors. Here we propose an ancillary study to the Molecular Transducers of Physical Activity Consortium (MoTrPAC), a multicenter NIH Common Fund project that aims to discover the molecular transducers ("molecular map") responsible for the beneficial health effects of physical activity and fitness in humans across the lifespan. Adding sleep assessment to the pediatric MoTrPAC study offers a transformative opportunity to begin to elucidate the interacting mechanisms of the fitness and sleep in humans during adolescent transition, a critical period of physical, neurobiological, and psychological development. This project proposes to evaluate a cohort of children and adolescents across maturational stages who complete the MoTrPAC protocol, which includes two phases: a Cross-Sectional phase, and an Endurance Exercise Intervention phase. Of note, this ancillary study does not change the existing MoTrPAC protocol/intervention and does not include any additional interventions, and is therefore not considered a clinical trial. This study will recruit subjects from the pediatric MoTrPAC study and evaluate phenotypic measures of sleep at the end of each MoTrPAC phase. Data obtained will allow exploration of fundamental mechanistic pathways underlying fitness-sleep interactions during adolescence and guide development of future clinical trials aimed at determining optimal sleep-exercise regimens for physical and mental health in various adolescent populations, including different racial/ethnic populations and medically at-risk groups. In addition, results from this study will be added to the MoTrPAC data repository, yielding a rich and unique dataset for further exploration of genomic, metabolomic, and p...