From left: Martin John Walsh, PhD; and Stuart Sealfon, MD
Empirical evidence shows that exercise improves and prevents a large number of diseases, but the scientific basis and molecular mechanisms responsible for these beneficial effects are largely unknown. Two researchers at the Icahn School of Medicine at Mount Sinai have been awarded $15.5 million by the National Institutes of Health (NIH) Common Fund—designated as the Physical Activity Genomics, Epigenomics/transcriptomics Site (PAGES)—to advance this knowledge by mapping the molecular signals between different parts of the body during physical activity.
Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology, Director of the Center for Advanced Research on Diagnostic Assays, and Chairman Emeritus of the Department of Neurology; and Martin John Walsh, PhD, Director for the Center of RNA Biology and Medicine, and a Professor of Pharmacological Sciences, Genetics and Genomic Sciences, and Pediatrics, will employ the latest genomic technologies in their investigation. They are part of a $170 million NIH program called the Molecular Transducers of Physical Activity Consortium (MoTrPAC), which involves more than two dozen academic research institutions around the country.
Using various genomic, epigenomic, transcriptomic, proteomic, and metabolomic technologies, Drs. Sealfon and Walsh, together with MoTrPAC, will analyze tissue and blood from 3,000 individuals in diverse racial, ethnic, gender, and age groups, and fitness levels. The samples will identify exercise-related chemical messengers and molecular responses that can provide the scientific basis for developing more effective individualized prescriptions of exercise, as well as the development of new drug therapies.
Where exercise has been studied, the benefits are measured in results such as less body fat, and lower cholesterol, sugar levels, and blood pressure. At molecular dimensions, the links between exercise and health remain mysterious.
“How is physical activity preventing or improving various cancers?” Dr. Sealfon asks. “We really don’t know the mechanisms.” The same holds true for Parkinson’s and Alzheimer’s diseases, depression, and other illnesses that have been shown in clinical studies to respond to exercise.
Based on their future findings, Drs. Sealfon and Walsh can foresee the creation of medications that mimic the signals released by exercising—so-called exercise mimetics—that would be particularly beneficial for patients with disorders that prevent or restrain their movement. According to NIH Director Francis S. Collins, MD, PhD, the current availability of advanced technology has made it possible to launch this bold new study. “This is the right time to take that technology forward,” he said. “We can now contemplate doing something that even a year ago would have been pretty hard to imagine.”
Physicians nowadays prescribe exercise routinely with particular attention to heart disease, weight control, and stress-related ailments. But, ultimately, the goal is to help them prescribe exercise on an individual basis. Such specificity would be based upon a clear understanding of the physical activity needed to assist each patient, rather than a one-size-fits-all approach.
The information gathered by all of the research sites involved in the consortium will be stored in a publicly accessible database that scientists can use to study almost every organ and tissue in the body.
Says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System: “To fully understand and subsequently transform clinical medicine’s use of physical activity for health management, a large-scale effort like this is imperative. Receiving this award is a testament to our outstanding faculty and our investment in genomics and systems biology research, which have positioned us to be able to contribute to this groundbreaking translational endeavor.”