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 initial goal set forth by NIH was to recruit 270 children (10-17 years of age) and 1980 sedentary adults (age 18 years or greater) that are randomized to endurance training (170 youth, 840 adults), resistance training (840 adults), or non-exercise controls (50 youth, 300 adults). 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 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 to 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 exercise adaptations and heterogeneity across age, gender, and minority groups. Altogether, this extension will allow 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.

PROJECT NARRATIVE While there are many important health benefits of physical activity, how exercise exerts its effects is not fully understood. A more comprehensive understanding of the molecular mechanisms underlying the responses to exercise would significantly impact public health. Continuation of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) will achieve its objective of generating a comprehensive map of the molecular responses to acute exercise and exercise training, with a long-range goal of elucidating the mechanisms by which exercise improves health.