The Molecular Transducers of Physical Activity in Humans program is the largest targeted NIH investment of funds into the mechanisms of how physical activity improves health and prevents disease. Through the program, researchers across the United States will receive about $170 million over six years (pending availability of funds) to study the molecular changes that occur during and after exercise and ultimately to advance our understanding of how physical activity improves and preserves health.

The Molecular Transducers of Physical Activity in Humans’ effort to uncover the molecular changes that occur in response to movement is expected to transform clinical medicine’s use of physical activity as a treatment and preventive strategy. Although researchers have demonstrated that physical activity is good for us in many ways, they know little about the molecules that cause these improvements. An analysis of NIH’s 2013 research grant portfolio, combined with a review of published scientific articles, found few studies examining how physical activity promotes overall health. Most are looking at exercise as a treatment or prevention strategy for a single health condition (e.g., addiction, mood disorders, dementia, diabetes, obesity, cancer, heart disease, stroke, osteoporosis, chronic pain).  

NIH recognized the need for a coordinated effort to assemble a comprehensive map of the proteins, peptides, circulating nucleic acids, lipids, hormones, and other molecules that change during or after exercise. These are the signals that are most likely to convey the effects of movement throughout the body.  In other words, they are probable “molecular transducers” of physical activity’s health benefits. All of the information will be stored in a publically accessible database that scientists can use to study almost every organ and tissue in the human body. Ultimately, the research findings resulting from this program could help scientists and clinicians define optimal physical activity recommendations for people at various stages of life, as well as develop precisely targeted regimens for individuals with particular health needs.

MoTrPAC is a national research consortium designed to discover and perform preliminary characterization of the range of molecular transducers (the ‘molecular map’) that underlie the effects of physical activity in humans. 19 grants support scientists at 25 universities and research centers across the country, all of whom will collaborate to identify many of the proteins, nucleic acids, lipids, hormones, and other signals that transmit the health effects of physical activity and to determine how variables such as age, sex, body composition, fitness level, and chronic exposure to exercise alter these molecular messengers.

Five interrelated components comprise the program’s Molecular Transducers of Physical Activity Consortium (MoTrPAC).

The Clinical Centers are central to the overall success of the project. MoTrPAC investigators around the country will recruit healthy males and females of all ages and of different races and ethnicities; some volunteers will be highly active at the beginning of the study, while others will have sedentary lifestyles. Researchers will collect blood, urine, and tissue samples from the adult volunteers who will perform resistance or aerobic exercises. These samples will be shared with colleagues at MoTrPAC Chemical Analysis Sites, who will extensively characterize a variety of molecules that change following exercise and may mediate the beneficial effects of physical activity. One center will manage a similar study in children to learn whether the molecules that relay activity’s health benefits differ as people mature.

Three Preclinical Animal Study Sites will conduct complementary experiments in rodents and provide tissues to the Chemical Analysis Sites that cannot be obtained from people (e.g., lung, liver, brain, and heart). The animal data will allow researchers to explore the functions, sources, and target tissues of the molecules identified in the samples provided by human volunteers.  

Blood, urine, and tissue samples will be extensively analyzed using high-throughput technologies that allow rapid identification of many different biological molecules from large numbers of samples. These services will be provided by Chemical Analysis Sites that specialize in genomics, epigenomics, metabolomics, proteomics and transcriptomics research.

Molecular data from the Chemical Analysis Sites and physiologic, morphometric, and metabolic data from the Clinical Centers and PASS will be integrated, stored, and shared by the Bioinformatics Center. The Bioinformatics Center also is responsible for developing a user-friendly database that any researcher can access to develop hypotheses regarding the mechanisms by which physical activity improves or preserves health.

A Consortium Coordinating Center will manage the development and implementation of the human and animal study protocols and coordinate the collection and distribution of data and biological samples from the studies during the project. It will organize, monitor, and support the MoTrPAC Steering Committee and any subcommittees that the Steering Committee may establish to ensure that all aspects of the clinical and animal protocols and the analysis plans contribute to the mapping of molecular changes in response to physical activity.  

The program has two overarching goals:

1. Assemble a comprehensive map of the molecular changes that occur in response to exercise and when possible relate these changes to the benefits of physical activity
2. Develop a user-friendly database that any researcher can access to develop hypotheses regarding the mechanisms whereby physical activity improves or preserves health

MoTrPAC is supported by the NIH Common Fund and is managed by a trans-agency Working Group representing multiple NIH Institutes and Centers, led by the NIH Office of Strategic Coordination, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Aging (NIA), and National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Data releases are accessible through the MoTrPAC Data Hub maintained by the MoTrPAC Bioinformatics Center (BIC). For updates when subsequent publicly accessible data become available, please contact the MoTrPAC Bioinformatics Center helpdesk at MoTrPAC Helpdesk.

The Molecular Transducers of Physical Activity Consortium (MoTrPAC) study encourages investigators to develop ancillary studies in conjunction with the MoTrPAC study and to involve other investigators, within and outside of MoTrPAC, in this process. More information can be found on the Ancillary Studies page of the MoTrPAC website maintained by the Consortium Coordinating Center.

More information about the MoTrPAC is available through the Molecular Transducers of Physical Activity in Humans web pages, maintained by the NIH Office of Strategic Coordination—The Common Fund at https://commonfund.nih.gov/MolecularTransducers/.