MoTrPAC Project Summary The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will discover and characterize the range of potential molecular transducers that underlie the health benefits of exercise in humans. MoTrPAC was launched in 2016 with six adult Clinical Centers and a pediatric Clinical Center that have collaborated to generate extensive Manuals of Operations to guide research protocols involving all aspects of clinical operations (Phase I). Phase II began in the fall of 2019 with all Clinical Centers demonstrating excellent progress toward initial recruitment goals and implementation of the protocol. The initial goal set forth by the Consortium was to recruit 270 children (10-17 years of age) and 1,980 sedentary adults (aged 18+ years of age) who are randomized to endurance exercise training (170 youth, 840 adults), resistance exercise training (840 adults), or no-exercise control (50 youth, 300 adults) interventions. Additional groups of highly active endurance trained (50 youth, 150 adults) or resistance trained (150 adults) individuals serve as comparator groups and do not undergo the MoTrPAC exercise interventions. The recruitment and enrollment approaches are sex balanced, with participants across a wide age range (10-17, 18-39, 40-59, and 60+ age groups) and of different races and ethnicity. Due to the COVID-19 pandemic, some MoTrPAC activities were suspended for more than a year, beginning in March 2020, with continued constraints through 2022. Despite the numerous challenges encountered as a result of the pandemic, recruitment activities at the adult and pediatric Clinical Centers have accelerated to a rate that is projected to successfully achieve the target enrollment numbers by the end of the new award period. This led the NIH Common Fund to release the current NOFO (RFA-RM-23-010) to provide MoTrPAC with funding to complete recruitment and follow-up for the clinical studies, including finishing mechanistic randomized controlled trials of sedentary adults and children and observational studies of highly active adults and children. This will enrich the participant cohorts that are critical to understand the heterogeneity of exercise adaptations across age, gender, and minority groups. This extension will enable MoTrPAC to complete the intended goals as originally envisioned and will provide a more complete public database of the health benefits of exercise and provide insight into how physical activity mitigates disease.