Molecular Transducers of Physical Activity in Humans

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The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to uncover, at the molecular level, how exercise improves and maintains the health of the body’s tissues and organs. Tracking exercise’s impact on biological molecules through time will help MoTrPAC researchers create a map of molecular changes in the body. Studies in three human tissues will be complemented by more extensive studies in an animal model, allowing many additional tissue types to be explored and substantially increasing the impact of the consortium. Researchers will use the molecular map to better understand how exercise affects people of different ages, sexes, body compositions, and fitness levels. In the future, it may also enable clinicians to make more specific exercise recommendations to patients when using exercise as an intervention to improve health.

When the MoTrPAC study is completed, it will be the largest research study examining the link between exercise and its improvement of human health. To gather the considerable amount of data needed to develop a molecular map of exercise-related changes in the body, MoTrPAC researchers are:

recruiting a diverse group of adult and child participants to study at Clinical Sites (CS),
performing rodent exercise studies at Preclinical Animal Study Sites (PASS),
identifying exercise-influenced biological molecules at Chemical Analysis Sites (CAS),
integrating all collected data at the Bioinformatics Center (BIC),
coordinating these many efforts, including storing and sharing samples, through the Consortium Coordinating Center (CCC).

The MoTrPAC program issued its first awards in December of 2016. During the first years of the program, the consortium developed the studies’ methods and other logistics. This included the establishment of clinical standards, data standards, animal study protocols, a data portal for researchers, and community outreach and recruitment materials and strategies. To date, the program has performed the full suite of planned animal studies and collected tissues for analysis. MoTrPAC clinical sites are currently recruiting both highly active and untrained participants. Please visit the consortium’s website for the latest news and updates regarding the study, or the data hub to access available data.

A lack of physical activity is at the root of many common chronic health problems. However, it is not understood what molecular changes are induced by movement or how they improve the function of different tissues and organs in the body. The NIH Common Fund's Molecular Transducers of Physical Activity in Humans program aims to catalogue the biological molecules affected by exercise in people, to assemble a comprehensive map of the molecular changes that occur in response to movement and, when possible, relate these changes to the benefits of physical activity. This molecular map will contain the many molecular signals that transmit the health effects of physical activity, and indicate how they are altered by age, sex, body composition, fitness level, and exposure to exercise. The program also aims to develop a user-friendly database that any researcher can access to develop hypotheses regarding the mechanisms whereby physical activity improves or preserves health, facilitating investigator-initiated studies and catalyzing the field of physical activity research.

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

MoTrPAC investigators at six adult Clinical Centers are recruiting approximately 2300 healthy adults for an exercise study. They are collecting blood and tissue samples from active and sedentary volunteers who will perform resistance or aerobic exercises. These materials are shared with colleagues at MoTrPAC Chemical Analysis Sites, who extensively characterize a variety of molecules that change following exercise. These molecules may transmit the benefits of physical activity to organs and tissues that are not directly involved in movement.

Another Clinical Center is focusing on the molecular changes that occur when children and adolescents exercise. Scientists and clinicians increasingly recognize that physical activity is an essential component of health, growth, and development, and there are critical periods when exercise can lead to long-term improvements in health. When combined with data from the six Centers focusing on adults, the research conducted at the pediatric Clinical Center will show whether the molecules delivering health benefits differ between children and adults or during different stages of development.

Research teams at three Preclinical Animal Study Sites are exploring the functions, sources, and target tissues of molecules that appear to be linked to physical activity’s health benefits. The rat exercise models used for these studies will complement the Clinical Centers’ work by allowing investigators to analyze tissues and organs that cannot be easily studied in people. Scientists also will use animal and cell models to investigate the roles of molecules of interest once the molecules are isolated and identified.

The Phase 2 Animal Study Sites joined the initial sites in 2020. Using MoTrPAC data, these three sites are also exploring the functions, sources, and target tissues of molecules that appear to be linked to physical activity's health benefits.

Investigators at seven Chemical Analysis Sites are extensively analyzing the human and rodent samples using various genomic, epigenomic, transcriptomic, proteomic, and metabolomic technologies. These cutting-edge tools, which allow for the rapid identification of many different biological molecules from large numbers of samples, will enable the characterization of a wide range of molecules that change following exercise and may mediate physical activity’s beneficial effects.

The Bioinformatics Center is responsible for establishing standards and protocols for data acquisition and storage, providing analytic tools for integrating and interrogating data generated through the Chemical Analysis Sites, and developing a user-friendly database that any researcher can access to develop hypotheses regarding the mechanisms whereby physical activity improves or preserves health.

The Consortium Coordinating Center manages study protocol development and implementation. It also coordinates the collection and distribution of data and biological samples during the project. It organizes, monitors, and supports 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 exercise.

MoTrPAC Centers Map