how it alters (for good) cells in all organs

Although it is already known that physical activity is one of the key factors in preventing chronic diseases and early mortality, the effects of exercise on cells are much more complex than previously imagined. A study published in the journal Nature by scientists from the Consortium of Molecular Transducers of Physical Activity (MoTrPAC) shows that the practice stimulates cellular and molecular changes in the 19 organs analyzed.

The study is part of an initiative aimed at mapping the effects of physical activity on the body so that, in the future, the information can be used for human health. For now, research is carried out on rats, monitored in the laboratory while undergoing various intense exercises.

The team, which includes scientists from the Massachusetts Institute of Technology, Harvard University and the National Institutes of Health in the United States, among others, evaluated the effects of physical activity on several organs, including the brain, heart and lungs. In all tissues studied, there were changes that help regulate the immune system, respond to cellular stress and control inflammation associated with various diseases.

Liver

According to the researchers, the data obtained so far gives important clues about health conditions that affect humans. For example, a possible explanation was found for the liver becoming less fatty during physical activity. This could help in the development of new treatments for non-alcoholic fatty liver disease.

Steve Carr, one of the project’s creators at MIT’s Broad Institute, said in a statement that the team hopes that the findings can one day be used to adapt exercise to a patient’s health condition. Or, develop treatments that mimic the effects of physical activity for those who are unable to exercise. Researchers have already begun studying the molecular effects in humans, Carr explained.

“It took a village of scientists with diverse scientific backgrounds to generate and integrate the enormous amount of high-quality data produced,” said Carr, co-senior author of the study. “This is the first whole-organism map that looks at the effects of training on several different organs. The resource produced will be extremely valuable and has already yielded many potentially new biological insights for future exploration.”

Adrenal

In total, the teams performed almost 10,000 tests to make around 15 million measurements in blood and 18 solid tissues. The data shows that exercise impacted thousands of molecules, with more extreme changes in the adrenal gland, which produces hormones that regulate many important processes, such as immunity, metabolism and blood pressure.

Scientists have also discovered differences in the effect of training on various organs depending on sex. Particularly those related to the immune response over time. In females, most of the associated molecules already showed changes between one and two weeks of training. In males, changes occurred between four and eight weeks.

Some responses were similar regardless of sex or organs. The researchers found, for example, that heat shock-related proteins, produced by cells in response to stress, were regulated in the same way in different tissues.

Target

Other changes, however, were specific. For example, the study showed changes in proteins involved in the production and storage of energy in the liver after exercise. These changes could make the organ less prone to disease and, at least theoretically, could be a target for future treatments for non-alcoholic cirrhosis.

“Even though the liver is not directly involved in exercise, it still undergoes changes that can improve health,” highlights Pierre Jean-Beltran, one of the study’s co-authors. “No one speculated that we would see these changes in the organ. Exercise is a very complex process and this is just the tip of the iceberg.”

Additional consortium studies are underway to study the effects of exercise in young and older adult rats, in addition to the short-term action of 30-minute physical activity sessions. The group has also started studies on humans and is recruiting around 1,500 people in the United States, of different profiles, to research the response to resistance training in children and adults.

Training as medicine

“We know that exercise has a therapeutic effect on many of the most chronic and debilitating diseases, but it is not yet like a medicine. This is because most medicines consist of well-defined molecules with well-defined mechanisms of action, pharmacokinetics and pharmacodynamics, and adverse effects. In the long term, science wants to understand the molecules and cells associated with high-resolution training, so that the practice of physical activity as medicine can become a reality”,

Jonathan Long, professor of pathology at Stanford University

Vaccine activates response against aggressive tumor

The treatment based on an mRNA vaccine, with a mechanism similar to that of Covid, reprogrammed the immune systems of four patients with glioblastoma, an aggressive brain cancer, paving the way for a larger phase 1 study. The research, from the University of Florida , is initial and many studies are still needed before the therapy becomes a reality, but the authors are excited about the results, published in the journal cell.

With standard treatment, which includes surgery, radiotherapy and chemotherapy, the average survival of a patient with the disease is 15 months. The vaccine described in the study has the potential to become a new treatment option, the authors claim. The next step will be to test it on a group of 24 adults and children with glioblastoma.

For the clinical trial described yesterday, four terminally ill adult patients were included, when there were no more therapeutic options. The vaccine, unlike immunizers that prevent viruses and bacteria, does not prevent the disease. What it does is recruit immune system cells to fight tumor cells more effectively than existing treatments.

“Onions”

In the University of Florida study, the personalized mRNA vaccine, using tumor cells from each patient, was combined with lipid nanoparticle technology. Oncologist Elias Sayour, senior author of the article, explains that the approach consists of applying a cluster of small pieces of brain cancer structures, “which wrap themselves around each other as if it were a bag full of onions.” “The reason we did this in the context of cancer is that these clusters alert the immune system in a much more profound way than single particles would.”

The scientist says that, in less than 48 hours, it was possible to observe a significant change in the immune system, with a much more active response than that observed before the vaccine was administered. “This was very surprising given how quickly it happened, and it showed us that we were able to very quickly activate the early part of the immune system, a key action in unlocking the downstream effects of the cells’ response to cancer.”

Before being tested on the four patients — all of whom have already died — the strategy was used in a trial with 10 dogs, all with terminal brain tumors. In animals, survival time was 139, compared to the 30 to 60 days typical for dogs with the disease. In the current study, the objective was not to measure survival, but to observe the vaccine’s action on the immune system.

If the next research has good results, the scientists hope to test the strategy on a group of 25 exclusively pediatric patients. “Maybe now we can have a combination with other immunotherapies,” says Sayour.