MoTrPAC Project Summary The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is designed to discover and characterize the range of molecular transducers that underlie the effects of exercise in humans. MoTrPAC was launched in 2016 with six adult clinical centers and a pediatric center that have collaborated to generate extensive Manual of Operations to guide research protocols involving all aspects of the clinical operations (Phase I). Phase II began in the fall of 2019 with all human clinical centers showing excellent progress towards initial recruitment goals and implementation of the protocol. The NIH that exercise initial goal set forth by was to recruit 270 children (10-17 years of age) and 1980 sedentary adults (age 18 years or greater) are andomized to endurance training ( 170 youth, 840 adults), resistance training (840 adults), or non- controls (50 youth, 300 adults). r An additional group of highly active endurance (50 youth, 150 adults) and resistance (150 adults) trained individuals serve as comparators and are not participating in the MoTrPAC exercise training programs. The recruitment and enrollment approach are sex balanced and with participants across a wide range of ages (10-17, 18-39, 40-59 and >60-year age groups) and of different races. Due to the COVID-19 pandemic, MoTrPAC activities were suspended for over a year (beginning in March 2020) with continued constraints through 2022. Despite encountered (adult) and study. the numerous challenges as a result of the pandemic, the human clinical centers have successfully enrolled ~80% and 95% (pediatric) of the highly active cohort, ~93% of cross-sectional (pediatric), and ~60% (adult) ~50% (pediatric) of the current target enrollment numbers in the randomized control trial portion of the This led to the NIH Common Fund to release the current NOFO (RFA-RM-23-010) to provide MoTrPAC with funding to complete mechanistic highly exercise extension more activity recruitment and follow-up for the clinical studies, including finishing randomized controlled trials of sedentary adults and children and observational studies of active adults and children. This wil l enrich the articipant cohorts that are critical to understand adaptations and heterogeneity across age, gender, and minority groups. Altogether, this will allow MoTrPAC to complete the intended goals as riginally envisioned and will provide a complete public database of the health benefits of exercise and provide insight into how physical mitigates disease. p o