CAMBRIDGE, Mass —We all know that exercise is good for our health, but the intricate ways in which physical activity affects our bodies at the cellular and molecular level have largely remained a mystery. Now, a seminal new study from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) has shed new light on the complex and far-reaching effects of exercise throughout the body.
Published in the magazine Nature, the study, which included a staggering 9,466 assays across 25 molecular platforms and four training time points, identified thousands of shared and tissue-specific molecular alterations in response to resistance training. These changes were observed in a wide range of biological pathways, including immune, metabolic, stress response and mitochondrial function.
Specifically, the researchers found that physical activity caused significant cellular and molecular changes in the 19 organs they studied, from the heart and brain to the lungs and liver. Simply put, exercise can benefit literally every fiber of your being!
It took a village of scientists with diverse scientific backgrounds to generate and integrate the large amount of high-quality data produced, says study co-lead author Steven Carr, senior director of the Broad Institutes’ Proteomics Platform, in a statement of press This is the first whole-organism map that looks at the effects of training on multiple different organs. The resource produced will be enormously valuable and has already produced many potentially new biological insights for further exploration.
One of the most striking findings was the widespread upregulation of the heat shock response in all tissues of the body. Heat shock proteins (HSPs), known to play a crucial role in cellular stress response and protein folding, were found to be prominently upregulated in response to exercise. This suggests that the protective effects of exercise may be mediated, in part, by the induction of HSPs, which could help prevent the accumulation of misfolded proteins and maintain cellular homeostasis.
The study also revealed tissue-specific adaptations to resistance training. For example, in the lung, the researchers observed a decrease in pathways related to inflammation, while in white adipose tissue, there was evidence of increased recruitment of immune cells. Heart and skeletal muscle showed a shared enrichment of mitochondrial metabolism pathways, highlighting the importance of improved energy production in these tissues.
The researchers’ interest was piqued when they saw that the small intestine showed a robust immune response to exercise, especially in female rats. Down-regulation of transcripts related to intestinal inflammation and decreased abundance of several immune cell markers suggest that resistance training may improve intestinal homeostasis and confer systemic anti-inflammatory effects. This finding is particularly relevant given the growing recognition of the gut-brain axis and its potential role in modulating overall health and well-being.
The study also shed light on metabolic adaptations to exercise across multiple tissues. The liver, in particular, showed the highest number of significantly enriched metabolite classes, followed by the heart, lung, and hippocampus. Changes in individual metabolites, such as trimethylamine-N-oxide, 1-methylhistidine, cortisol, and 1-methylnicotinamide, provided information on the functional alterations induced by exercise training.
Although the liver is not directly involved in exercise, it still undergoes changes that could improve health. No one speculated that we would see these acetylation and phosphorylation changes in the liver after exercise, explains study co-author Pierre Jean-Beltran, a postdoctoral researcher in the Carrs group at the Broad. This highlights why we deploy all these different molecular modalities: exercise is a very complex process, and this is only the tip of the iceberg.
Perhaps one of the most interesting aspects of this study is its potential to inform the development of targeted interventions that mimic the health benefits of exercise. By identifying the key molecular pathways and regulators involved in the adaptive response to resistance training, researchers may be able to design drugs or therapies that activate these pathways in individuals who are unable to participate in regular physical activity. Basically, knowing exactly how exercise benefits the human body is bringing science one step closer to creating an exercise pill.
Two or three generations of research associates matured in this consortium project and learned what it means to carefully design a study and process samples, adds study co-author Hasmik Keshishian, senior leader of the Carrs group. We are now seeing the results of our work: biologically insightful findings that arise from the high-quality data we and others have generated. This is really satisfying.
The MoTrPAC team has made all animal data available in a public online repository, ensuring that other scientists can access and build on their findings. They have also begun human studies, recruiting about 1,500 individuals of different ages, sexes, backgrounds and activity levels for a clinical trial to study the effects of endurance and resistance exercise in children and adults.
StudyFinds Matt Higgins contributed to this report.
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