Why is exercise beneficial for you?

Using genomics, proteomics, metabolomics and protein immunoassays to study the effects of cardiovascular and other fitness training conditions in rats

The first data set is from rats that completed one to eight weeks of treadmill training, and had blood and tissue samples collected at the end. The researchers pinpointed thousands of molecular changes throughout the rats’ bodies, many of which could have a protective effect on health, such as dialling down inflammatory bowel disease and tissue injury2. A separate study3 found that the effects of endurance training differed across sexes: markers associated with the breakdown of fat increased in male fat tissue, driving fat loss, whereas female fat tissue showed an increase in markers related to fat-cell maintenance and insulin signalling, which might protect against cardiometabolic diseases. A third study4 found that exercise alters the expression of genes linked to diseases such as asthma, and could help to trigger similar adaptive responses.

Whole blood, plasma and 18 solid tissues were analysed using genomics, proteomics, metabolomics and protein immunoassay technologies, with most assays performed in a subset of these tissues (Fig. 1b and Extended Data Fig. 1e,f). Specific details for each omic analysis are provided in Extended Data Fig. 2, Methods, Supplementary Discussion and Supplementary Table 1. The heart, lungs, hippocampus, and liver are the most diverse of the assays performed because of their available tissue quantity and biological relevance. More than 697,000 non-epigenetic and 14,335,600 epigenetic assays were created from 9,466 tests across the various combinations of tissues and platforms.

The Impact of Exercise on the Human Body – A Multiomic Profiling Study of a Mouse Cascade with Secreted Carbolesterases

When Bente Klarlund Pedersen wakes up in the morning, the first thing she does is pull on her trainers and go for a 5-kilometre run — and it’s not just about staying fit. “It’s when I think and solve problems without knowing it,” says Klarlund Pedersen, who specializes in internal medicine and infectious diseases at the University of Copenhagen. It is important for my well-being.

After people ran on a treadmill, he and his colleagues took blood samples from 36 of them, aged 40 to 75 years old. The team used multiomic profiling to measure more than 17,000 molecules and half showed important changes after exercise. They found that exercise triggered an elaborate echocardiography of biological processes such as energy metabolism, oxidative stress and inflammation. Creating a catalogue of exercise molecules is an important first step in understanding their effects on the body, says Snyder.

But researchers are just beginning to work out the meaning of this cacophony of crosstalk, says Atul Shahaji Deshmukh, a molecular biologist at the University of Copenhagen. “Any single molecule doesn’t work alone in the system,” says Deshmukh, who enjoys mountain biking during the summer. An entire network that functions together.

The findings also showed that after exercise, the mice’s liver cells squeezed out several types of carboxylesterase enzyme, which are known to ramp up metabolism. Long and his colleagues genetically tinkered with mice so that they gained weight when fed a diet of fat. They ran on a treadmill and had more endurance than before. “The improvement in exercise performance by these secreted carboxylesterases was not known before,” says Long, whose weekly exercise regime involves swimming and lifting weights. He adds that if the enzymes could be produced in the right quantities and purity, they could possibly be used as exercise-mimicking compounds.

It could offer clues about how physical activity can benefit people with chronic illnesses. She believes that you can prescribe exercise as you can write a medicine.

Exercise is a fundamental thread in the human evolutionary story. Humans have a lifestyle that demands walking long distances, carrying large amounts of food and occasionally running from threats, even though they evolved as a more sedentary species.

Researchers have been looking at the biological changes that occur during exercise for more than a century. In 1910, pharmacologist Fred Ransom at the University of Cambridge, UK, discovered that skeletal muscle cells secrete lactic acid, which is created when the body breaks down glucose and turns it into fuel5. And in 1961, researchers speculated that skeletal muscle releases a substance that helps to regulate glucose during exercise6.

More clues were in store. After collecting blood samples from runners before and after a marathon, they found that several cytokines spiked immediately after exercise and that many remained elevated for up to four hours. A key player in the body’s defence response,IL 6 is a multi-billion dollar industry and was one of the cytokines included. The inflammatory agent IL-6 was discovered to be produced by contracting muscles during exercise, as the umbrella term for compounds produced in response to exercise.

Exercise is a balancing act as well. The damaging effect on the cellular structures is counterbalanced by certainmolecules. When mitochondria — the powerhouses that supply energy in cells — ramp up production during exercise, they also produce more by-products called reactive oxygen species (ROS), which, in excessive amounts, can damage proteins, lipids and DNA. The ROS kick start a horde of protective processes, offsetting their toxic effects and fortifying cellular defences.

Other studies have probed how exercise affects cell types. A 2022 study in mice led by Jonathan Long, a pathologist at Stanford University, identified more than 200 types of protein that were expressed differently by 21 cell types in response to exercise10. The researchers were expecting to find that cells in the liver, muscle and bone would be most sensitive to exercise, but to their surprise, they found that a much more widespread type of cell, one that appears in many tissues and organs, showed the biggest changes in the proteins that it cranked out or turned down. The findings suggest that more cell types shift gears during a workout than was previously thought, although what these changes mean for the body is still an open question, says Long.

When working out, distant organs and tissues communicate with each other. Mark Febbraio, a former athlete and now an exercise scientist at the University of Victoria, believes that EVs could be part of the mechanisms behind organ and tissue crosstalk. In 2018, Febbraio and his team inserted tubes into the femoral arteries of 11 healthy men and drew blood before and after they rode an exercise bike at an increasing pace for an hour. They found a spike in levels of more than 300 types ofprotein after exercising, but not at rest.

Most of the EVs ended up in liver cells when the team collected them from the treadmills that the mice had run on. In a separate mouse study that is yet to be published, Febbraio and his colleagues found some interesting clues about the contents of these EVs. A big question is whether EVs also deposit genetic material into different cells, and if so, what that means for the body. “We still don’t know a great deal,” he says.

Source: Why is exercise good for you? Scientists are finding answers in our cells

What Exercise Does Matter: An Empirical Study of the Effects of Age, Gender, and Ethnicity on Human Development and Health

A goal is to uncover the reasons why exercise has varied effects on people of different genders, ages, and ethnic background. “It’s very obvious that some people benefit better than others,” he says.