A molecular map of your entire body explains why exercise is so good for you

Exercise isn’t just about increasing muscle strength, improving heart health, and lowering blood sugar levels; it’s also linked to a host of other health benefits. But how does a regular run on the treadmill, a steep bike ride, or a brisk walk at lunchtime yield such a dizzying array of health benefits?

We're closer to answering that question, thanks to a massive new study from Stanford School of Medicine. The researchers took nearly 10,000 measurements across nearly 20 types of tissue to see the effects of eight weeks of endurance exercise on lab rats trained to run on rodent-sized treadmills.

Their findings highlight the striking effects of exercise on the immune system, stress response, energy production and metabolism. They found significant links between exercise and molecules and genes already known to play a role in a variety of human diseases and tissue repair.

The study is one of a series of papers published May 1 by members of a multidisciplinary research team designed to lay the foundation for understanding – at the whole-body and molecular level – how our tissues and cells respond to exercise.

“We all know that exercise is good for us,” says pathology professor Stephen Montgomery, PhD. “But we know little about the molecular signals that occur throughout the body when people exercise, or how they might be altered by training. Our study is the first to look at molecular changes on a whole-body scale, from proteins to genes, metabolites, fats, and energy production. It’s the broadest profiling of the effects of exercise to date, and it creates an important map of how it changes the body.”

Montgomery, who is also a professor of genetics and biomedical data science, is the senior author of the paper published in the journal Nature.

A coordinated view of exercises

The researchers involved in the study and other concurrent publications are part of a national group called the Molecular Transducers of Physical Activity Consortium, or MoTrPAC, organized by the National Institutes of Health. The initiative was launched in 2015 to study in detail how exercise improves health and prevents disease.

The Stanford Medicine team has done much of the heavy lifting, studying the effects of eight weeks of endurance training on the expression of genes (transcriptome), proteins (proteome), fats (lipidome), metabolites (metabolome), the pattern of chemical tags placed on DNA (epigenome), the immune system, and more.

They ran 9,466 tests on multiple tissues in rats that were trained to run increasing distances, and compared the results with those of rats that were lazing around in their cages. They focused on leg muscles, heart, liver, kidneys, and white adipose tissue (the type of fat that accumulates as you gain weight); other tissues included lungs, brain, and brown adipose tissue (a more metabolically active type of fat that helps burn calories).

The combination of multiple analyses and tissue types yielded results numbering in the hundreds of thousands for non-epigenetic changes and more than 2 million distinct changes in the epigenome. These results will keep scientists busy for years to come.

While this study primarily served to create a database for future analysis, some interesting results have already emerged. First, they noted that the expression of 22 genes changed with exercise in all six tissues they focused on.

Many of the genes were involved in so-called heat shock pathways, which stabilize protein structure when cells are exposed to stress, including temperature changes, infection, or tissue remodeling. Other genes were involved in pathways that lower blood pressure and increase the body's sensitivity to insulin, which lowers blood sugar levels.

The researchers also noted that the expression of several genes linked to type 2 diabetes, heart disease, obesity and kidney disease was reduced in the exercising rats compared to their sedentary peers, clearly indicating a link between their research and human health.

Gender differences

Finally, they found sex differences in how various tissues in male and female rats responded to exercise. Male rats lost about 5 percent of their body fat after eight weeks of exercise, while females did not lose much fat. (They did, however, maintain their starting body fat percentage, while sedentary females gained an additional 4 percent fat over the course of the study.)

But the biggest difference was in gene expression in the rats' adrenal glands. After a week, genes linked to the production of steroid hormones such as adrenaline and energy production increased in male rats but decreased in female rats.

Despite these early, tantalizing associations, researchers caution that exercise science is far from complete. In fact, it’s just getting started. But the future looks promising.

“In the long term, it’s unlikely that we’ll find one magic intervention that replicates everything exercise can do for a person,” Montgomery said. “But we can get closer to the idea of precision exercise — tailored recommendations based on a person’s genetics, gender, age, or other medical conditions to achieve beneficial whole-body responses.”