Any amount of physical activity is better than none. In fact, 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 will recruit approximately 2700 healthy adults for an exercise study. They will collect blood and tissue samples from active and sedentary volunteers who will perform resistance or aerobic exercises. These materials will be shared with colleagues at MoTrPAC Chemical Analysis Sites, who will extensively characterize a variety of molecules that change following exercise and may transmit the benefits of physical activity to organs and tissues that are not directly involved in movement. The adult Clinical Centers are led by
- Marcas Bamman at the University of Alabama at Birmingham Center for Exercise Medicine, Bret Goodpaster at the Translational Research Institute for Metabolism and Diabetes in Orlando, Florida, and Scott Trappe at the Ball State University Human Performance Laboratory (U01AR071133)
- John Jakicic at the University of Pittsburgh (U01AR071130)
- Wendy Kohrt at the University of Colorado, Denver (U01AR071124)
- William Kraus at Duke University, in partnership with Joseph Houmard at East Carolina University and Barbara Nicklas at Wake Forest Baptist Medical Center (U01AR071128)
- Blake Rasmussen at University of Texas Medical Branch at Galveston and Nicolas Musi at the University of Texas Health Science Center at San Antonio (U01AR071150)
- Eric Ravussin and Tuomo Rankinen at Louisiana State University’s Pennington Biomedical Research Center (U01AR071160)
Another Clinical Center (U01AR071158), led by Dan Cooper and Shlomit Radom-Aizik at the University of California-Irvine, will focus 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 University of California-Irvine will show whether the molecular transducers of health benefits differ in children and in adults and during different stages of development.
Research teams at three Preclinical Animal Study Sites will explore 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 studied in people. Scientists also will use animal and cell models to investigate the roles of potential transducers once the molecules are isolated and identified. The groups are led by
- Sue Bodine and Keith Barr at the University of California at Davis (U01AG055133)
- Karyn Esser at the University of Florida (U01AG055137)
- Laurie Goodyear at the Joslin Diabetes Center in Boston (U01AG055135)
Investigators at seven Chemical Analysis Sites will extensively analyze 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 teams are led by
- Joshua Adkins at Pacific Northwest National Laboratory (U24DK112349)
- Charles Burant and Jun Li at the University of Michigan (U24DK112342)
- Robert Gerszten, Clary Clish, and Stephen Carr at the Broad Institute/Beth Israel Deaconess Medical Center and Chris Newgard at Duke University (U24DK112340)
- Dean Paul Jones at Emory University (U24DK112341)
- Sreekumaran Nair and Ian Lanza at Mayo Clinic, Rochester (U24DK112326)
- Stuart Sealfon and Martin Walsh at Icahn School of Medicine at Mount Sinai (U24DK112331)
- Michael Snyder and Stephen Montgomery at Stanford University (U24DK112348)
The Bioinformatics Center (U24EB023674), led by Euan Ashley at Stanford University, 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 (U24AR071113), led by Marco Pahor at the University of Florida, Michael Miller at Wake Forest Baptist Medical Center, Walter Rejeski at Wake Forest University, and Russell Tracy at the University of Vermont, will manage study protocol development and implementation and will coordinate the collection and distribution of data and biological samples 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 exercise.