Metamorphosis: Exercise triggers molecular changes in major organs

While the benefits of exercise on overall health are broadly recognized, the intricate biological responses triggered at a cellular level by physical activity have only recently been explored in depth.

A landmark study involving an array of scientific experts from various U.S. institutions has significantly advanced our understanding of this complex phenomenon.

The scientists employed a range of sophisticated techniques to investigate the molecular changes that occur across different organs during periods of intense exercise.

The study revealed that physical activity influences a multitude of cellular and molecular mechanisms across all 19 organs analyzed in the rats used for the experiment.

The findings show that the body’s adaptation to exercise extends well beyond muscle growth and cardiovascular health, encompassing significant changes in organs such as the heart, brain, and lungs.

Insights into the molecular benefits of exercise

The study was a part of an ambitious initiative, the Molecular Transducers of Physical Activity Consortium (MoTrPAC), which began in 2016.

This project brings together researchers from prestigious institutions such as the Broad Institute of MIT and Harvard, Stanford University, and the National Institutes of Health.

The consortium involved leading scientists who envisioned a comprehensive analysis of exercise’s effects at the molecular level. The project was originally conceived of by Steve Carr, senior director of Broad’s Proteomics Platform.

Focus of the research

“Regular exercise provides wide-ranging health benefits, including reduced risks of all-cause mortality, cardiometabolic and neurological diseases, cancer and other pathologies,” wrote the study authors.

“Exercise affects nearly all organ systems in either improving health or reducing disease risk, with beneficial effects resulting from cellular and molecular adaptations within and across many tissues and organ systems.” 

“Various ‘omic’ platforms (‘omes’) including transcriptomics, epigenomics, proteomics and metabolomics, have been used to study these events. However, work to date typically covers one or two omes at a single time point, is biased towards one sex, and often focuses on a single tissue, most often skeletal muscle, heart or blood, with few studies considering other tissues.”

“Accordingly, a comprehensive, organism-wide, multi-omic map of the effects of exercise is needed to understand the molecular underpinnings of exercise training-induced adaptations.” 

Enormously valuable resource

The expansive study not only scrutinized tissues from various organs but also revealed how these organs contribute to regulating immune response, stress reactions, and even pathways related to chronic conditions like inflammatory liver disease and heart disease.

“It took a village of scientists with distinct scientific backgrounds to generate and integrate the massive amount of high quality data produced,” said Carr.

“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.”

Molecular changes from exercise

One of the more significant revelations was the discovery of molecular changes that might explain why the liver becomes less fatty during exercise. Such insights could pave the way for new treatments for conditions like non-alcoholic fatty liver disease.

In addition, the research team hopes their findings can eventually be used to personalize exercise plans based on an individual’s health status or to develop therapeutic strategies that mimic the benefits of physical activity for those unable to exercise regularly.

The data from this extensive study have been made available in an online public repository, allowing other researchers to access and utilize this information for further study.

Exercise impacts thousands of molecules

The collective effort of the teams involved required significant coordination, as highlighted by Clary Clish, one of the lead researchers. “The amount of coordination that all of the labs involved in this study had to do was phenomenal.”

This meticulous planning allowed for nearly 10,000 assays, resulting in approximately 15 million measurements on blood and solid tissues.

Through these efforts, the researchers have observed that exercise impacts thousands of molecules, with notable changes occurring in the adrenal gland, which plays a crucial role in regulating immunity, metabolism, and blood pressure.

Additionally, the study uncovered sex-specific differences in immune response, providing a nuanced understanding of how exercise affects males and females differently over time. Most immune-signaling molecules unique to females showed changes in levels between one and two weeks of training, while those in males showed differences between four and eight weeks, noted the experts.

Foundation for future research

As research continues, these insights offer a promising frontier for enhancing human health through a more refined understanding of the molecular benefits of exercise.

The pioneering study not only furthers our understanding of the biological responses to physical activity but also sets the stage for tailored health interventions that could one day revolutionize personal health and wellness.

“Altogether, this multi-omic resource serves as a broadly useful reference for studying the milieu of molecular changes in endurance training adaptation and provides new opportunities to understand the effects of exercise on health and disease,” concluded the researchers.

The study is published in the journal Nature.

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