Molecular Transducers of Physical Activity in Humans

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).

Clinical Centers

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.

Preclinical Animal Study Sites

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.

Chemical Analysis Sites

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.

Bioinformatics Center

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.

Consortium Coordinating Center

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.