Woman doing bent over rows while lifting weights at the gym

(Photo by Alora Griffiths on Unsplash)

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 remained largely a mystery. Now, a seminal new study by the Molecular Transducers of Physical Activity Consortium (MoTrPAC) has shed new light on the complex and far-reaching effects of exercise on the entire body.

Published in the journal Nature, the study, which included an astounding 9,466 assays across 25 molecular platforms and four training time points, identified thousands of shared and tissue-specific molecular alterations in response to endurance training. These changes were observed in a wide range of biological pathways, including immune, metabolic, stress response, and mitochondrial function.

Specifically, researchers discovered physical activity caused significant cellular and molecular changes in all 19 of the organs they studied, from the heart and brain to the lungs and liver. Simply put, working out can literally benefit every fiber of your being!

“It took a village of scientists with distinct scientific backgrounds to generate and integrate the massive amount of high quality data produced,” says co-senior study author Steven Carr, senior director of the Broad Institute’s Proteomics Platform, in a media release. “This is the first whole-organism map looking at the effects of training in multiple different organs. The resource produced will be enormously valuable, and has already produced many potentially novel biological insights for further exploration.”

Researchers discovered physical activity caused significant cellular and molecular changes in all 19 of the organs they studied (Credit: Ricardo Job-Reese, Broad Communications)

One of the most striking findings was the widespread regulation of the heat shock response across all of the body’s tissues. Heat shock proteins (HSPs), which are 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 endurance training. For example, in the lung, researchers observed a decrease in inflammation-related pathways, while in white adipose tissue, there was evidence of increased immune cell recruitment. The heart and skeletal muscle showed a shared enrichment of mitochondrial metabolism pathways, highlighting the importance of improved energy production in these tissues.

Researchers’ interest piqued when they saw that the small intestine exhibited a robust immune response to exercise, particularly in female rats. The downregulation of transcripts related to gut inflammation and the decreased abundance of various immune cell markers suggest that endurance training may improve gut 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 the metabolic adaptations to exercise across multiple tissues. The liver, in particular, showed the greatest 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 insights into the functional alterations induced by exercise training.

“Even though the liver is not directly involved in exercise, it still undergoes changes that could improve health. No one speculated that we’d see these acetylation and phosphorylation changes in the liver after exercise training,” explains co-first study author Pierre Jean-Beltran, a postdoctoral researcher in Carr’s group at Broad. “This highlights why we deploy all of these different molecular modalities — exercise is a very complex process, and this is just the tip of the iceberg.”

Woman tired and sweaty from long run and workout
Knowing exactly how exercise benefits the human body is moving science one step closer to creating an exercise pill. (Photo by Jacob Lund on Shutterstock)

Perhaps one of the most exciting 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 endurance training, researchers may be able to design drugs or therapies that activate these pathways in individuals who are unable to engage in regular physical activity. Basically, knowing exactly how exercise benefits the human body is moving science one step closer to creating an exercise pill.

“Two or three generations of research associates matured on this consortium project and learned what it means to carefully design a study and process samples,” adds study co-author Hasmik Keshishian, a senior group leader in Carr’s group. “Now we are seeing the results of our work: biologically insightful findings that are yielding from the high quality data we and others have generated. That’s really fulfilling.”

The MoTrPAC team has made all of the animal data available in an online public repository, ensuring that other scientists can access and build upon their findings. They have also begun human studies, recruiting about 1,500 individuals of diverse ages, sexes, ancestries, and activity levels for a clinical trial to study the effects of both endurance and resistance exercise in children and adults.

StudyFinds’ Matt Higgins contributed to this report.

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