We all know that exercise is good for us.
A brisk walk of about an hour a day can prevent chronic diseases, such as heart or blood vessel problems and type 2 diabetes. Regular exercise delays memory loss due to aging, boosts the immune system, reduces ‘stress and can even increase lifespan.
For decades, scientists have tried to understand why. Throughout the body, our organs and tissues release a wide variety of molecules during and even after exercise to reap its benefits. But no molecule works alone. The hard part is understanding how they collaborate in networks after the exercise.
Enter the Molecular Transducers of Physical Activity Consortium (MoTrPAC) project. Created nearly a decade ago and funded by the National Institutes of Health (NIH), the project aims to create comprehensive molecular maps of how genes and proteins change after exercise in both rodents and humans. Rather than focusing on single proteins or genes, the project takes a Google Earth approach to seeing the big picture.
It’s not just out of scientific curiosity. If we can find important molecular processes that trigger the benefits of exercise, we could mimic these reactions with drugs and help people who can’t exercise with a pill.
This month, the project announced multiple results.
In one study, scientists created an atlas of body changes before, during and after exercise in rats. In total, the team collected nearly 9,500 samples from various tissues to examine how exercise changes gene expression throughout the body. Another study detailed gender differences after exercise. A third team mapped exercise-related genes to those associated with disease.
According to the project’s NIH website: When the MoTrPAC study is completed, it will be the largest research study examining the link between exercise and its improvement in human health.
work on it
Our fabrics are chats. The gut talks to the brain through a vast maze of molecules. Muscles pump out proteins to fine-tune immune system defenses. The liquid plasma portion of blood can transfer the learning and memory benefits of running when injected into couch potato mice and delay cognitive decline.
Over the years, scientists have identified individual molecules and processes that might mediate these effects, but the health benefits are likely due to networks of molecules working together.
MoTrPAC was launched to fill an important gap in exercise research, former NIH Director Dr. Francis Collins said in a 2020 press release. It shifts the focus to a specific organ or disease to a fundamental understanding of exercise at the molecular level, which can lead to personalized and prescribed exercise regimens based on individual needs and traits.
The project has two arms. One observes rodents before, during and after the wheel to build comprehensive maps of the molecular changes due to exercise. These maps aim to capture gene expression along with metabolic and epigenetic changes in multiple organs.
Another arm will recruit approximately 2,600 healthy volunteers aged 10 to over 60. With a large number of participants, the team hopes to account for variation between people and even identify differences in the body’s response to exercise based on age, gender or race. Volunteers will undergo 12 weeks of exercise, either resistance training such as long-distance running or weight lifting.
Together, the goal is to detect how exercise affects cells at the molecular level in various types of tissue, blood, fat and muscle.
Encyclopedia of exercises
Last week, MoTrPAC released an initial wave of findings.
In one study, the group collected blood and 18 different tissue samples from adult rats, both male and female, as they happily functioned for a week to two months. The team then examined how the body changes with exercise by comparing working rats with couch potato rats as a reference. The physical training increased the rats’ aerobic capacity, the amount of oxygen the body can use, by about 17 percent.
The team then analyzed the molecular fingerprints of exercise in whole blood, plasma and 18 solid tissues, including heart, liver, lung, kidney, adipose tissue and the hippocampus, a brain region associated with memory. They used an impressive array of tools that, for example, captured changes in overall gene expression and the epigenetic landscape. Others mapped differences in the body’s protein, fat, immune system, and metabolism.
In total, datasets were generated from 9,466 assays in 211 combinations of tissues and molecular platforms, the team wrote.
Using an AI-based method, they integrated the results over time into a comprehensive molecular map. The map identified multiple molecular changes that could dampen liver disease, inflammatory bowel disease, and protect against heart health and tissue injury.
All of this represents the first whole-organism molecular map that captures how exercise changes the body, the team wrote. (All data is free scan.)
Venus and Mars
Most previous studies of exercise in rodents focused on males. What about the ladies?
After analyzing the MoTrPAC database, another study found that exercise changes the body’s molecular signaling differently depending on biological sex.
After running, the female rats activated white fat-type genes under the skin related to insulin signaling and the body’s ability to form fat. Meanwhile, the men showed molecular signatures of an accelerated metabolism.
With consistent exercise, male rats rapidly lost fat and weight, while female rats maintained their curves but with improved insulin signaling, which could protect them from heart disease.
A third study integrated gene expression data collected from exercised rats with databases of disease-relevant genes previously found in humans. The goal is to link training-related genes in a particular organ or tissue to a disease or other health outcome, what the authors call trait-tissue-gene triplets. In total, they found 5,523 triplets to serve as a valuable starting point for future research, they wrote.
We were only scratching the surface of the complex puzzle that is exercise. Through extensive mapping efforts, the project aims to customize exercise regimens for people with chronic illnesses or identify key druggable components that could confer some of the health benefits of exercise with a pill.
This is an unprecedented large-scale effort to begin to explore in extreme detail the biochemical, physiological and clinical impact of exercise, Dr. Russell Tracy of the University of Vermont, a member of MoTrPAC, said in a statement from press
Image credit: Fitsum Admasu / Unsplash
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