The health benefits of exercise have long been recognized, but it's not fully understood how it changes the body at the molecular level. The new study, published in the journal Nature , looked at 19 organs in mice. The results show that the body's response to extended exercise is more complex and wide-ranging than previously thought. Prolonged physical activity in these animals caused profound changes in RNA, proteins and metabolites in nearly every tissue, providing clues to many human conditions, the authors said. To reach their conclusions, the scientists used a battery of laboratory techniques to analyze molecular changes in mice subjected to weeks of intensive exercise. They looked at tissues including the heart, brain and lungs, and found that each organ changed in ways that helped the body regulate the immune system, respond to stress and control pathways linked to inflammatory diseases of the liver, heart and connective tissues. The research was led by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), which includes scientists from the Broad Institute of MIT and Harvard, Stanford University and the U.S. National Institutes of Health. "This is the first organism-wide map of how exercise training reprograms multiple organs. The resource will be extremely valuable and has already yielded many potentially novel biological insights for further exploration," said Steve Carr of the Broad. "There are a variety of different assays on the same tissues, and that gives a comprehensive view of how all these different molecular layers contribute to the exercise response," said Natalie Clark, a computational scientist at the Broad. In all, nearly 10,000 assays were performed, making some 15 million measurements in blood and 18 solid tissues, the Broad Institute said in a statement. The scientists found that exercise affected thousands of molecules, with the most extreme changes occurring in the adrenal gland, which produces hormones that regulate many important processes, such as immunity, metabolism and blood pressure. The study also revealed sex differences in several organs, particularly in the immune response. Most of the immune signaling molecules unique to females changed within one to two weeks of exercise training, while those in males showed differences after four to eight weeks. To their surprise, the scientists found an increase in the acetylation of mitochondrial proteins, involved in energy production, and in a phosphorylation signal that regulates energy storage, in both the liver and the body as a whole, that changed with exercise. These modifications could help make the liver less fatty and less prone to disease with exercise, and could offer a target for future treatments for nonalcoholic fatty liver disease. "Even though the liver is not directly involved in exercise, it undergoes changes that could improve its health. No one expected to see these acetylation and phosphorylation changes with exercise training," said Jean Beltran, who added: "Exercise is a very complex process, and this is just the tip of the iceberg." The authors, who have made their data available to the entire scientific community, hope their findings could one day be used to tailor exercise to an individual's health status or to develop treatments that mimic the effects of physical activity. See Also: mRNA vaccine elicits strong immune response against brain tumor (Portuguese version)