Exercise may be the key to a younger, sharper immune system

The research was funded by FAPESP and published in Scientific reportsfocuses on natural killer (NK) cells, a type of white blood cell (lymphocyte) that targets infected or damaged cells, including cancer cells. As key players in the body’s first line of defense, NK cells detect and neutralize invading pathogens. The team analyzed samples from nine participants with an average age of 64 years, and divided them into two groups: one untrained and the other made up of individuals who had participated in endurance exercises for years.

“In a previous study, we found that obesity and a sedentary lifestyle can lead to a process of premature aging of defense cells. This made us want to investigate the other side of the story, namely whether an older person who has been doing endurance exercise for more than 20 years might have a better prepared immune system. And that is indeed what we found. In these individuals, the natural killer cells worked better in meeting the inflammatory challenge, in addition to using energy more effectively.” Bigger. Efficiently. “It’s as if exercise also trains the immune system,” says Lucille Minuzzi, a visiting researcher at Justus Liebig University Giessen (JLU) in Germany.

Minuzzi’s work forms part of his postdoctoral research, and contributes to a broader project led by the University of São Paulo State (UNESP) in Brazil, also supported by FAPESP.

The results suggest that sustained endurance training helps regulate inflammation over time. “When we compared the cells of trained elderly people with those of non-athletes of the same age, we found that those with a history of endurance exercise had fewer inflammatory markers and more anti-inflammatory markers,” says Fabio Lira, professor at the Faculty of Science and Technology (FCT-UNESP), Presidente Prudente Campus. “This means that, compared to non-athletic elderly people, they had much better control of inflammation.” coordinator.

Lira points out that the immune system is affected by many lifestyle factors, including sleep quality, nutrition, vaccination, stress, inactivity, and some medications that suppress immune activity. “Physical exercise is one such factor that can benefit the immune system, and in this research project, we are investigating how the immune response is modified over time,” he says.

Changes in the cell

The team also examined how natural killer cells function and metabolize energy in response to inflammation. They exposed these cells from trained and untrained elderly people to pharmacological agents such as propranolol and rapamycin to observe their effects.

“Trained older individuals show more efficient and adaptable immunity, with greater metabolic control and less tendency to cellular exhaustion. Regular physical exercise appears to positively modulate both adrenergic sensitivity and cellular energy sensors, promoting a more balanced and less inflammatory response to external stimuli,” says Minozzi.

Propranolol is a drug that blocks the adrenergic pathway – a network of nerve and hormonal signals that release neurotransmitters such as adrenaline and norepinephrine – and has been used to study the role of this pathway in natural killer cell activity. In contrast, rapamycin inhibits the mTORC1 signaling pathway, which controls cell growth and proliferation. In the experiment, high doses of rapamycin (100 ng/ml) changed the properties of NK cells and reduced their growth in laboratory conditions.

“In both cases, even with blocking of signaling pathways, the NK cells of the trained elderly were able to maintain their immune function, while the cells of the untrained individuals showed cellular exhaustion or failure of the inflammatory response. This means that long-term endurance training is associated with protective ‘immunometabolic’ adaptations in the NK cells of the elderly. In other words, they become The cells are more mature and functional, less senescent, and more metabolically prepared to respond to inflammatory or pharmacological stressors,” the researcher says.

Inflammatory response

In another study, the same group of researchers compared the immune response of young and professional athletes before and after an acute exercise session. To do this, they analyzed data from whole blood and PBMC (the single nuclear part of the blood formed by lymphocytes and monocytes, which include NK cells) from 12 major athletes (with an average age of 52 years and more than 20 years of continuous training) and compared them with data from young athletes (with an average age of 22 years and more than 4 years dedicated to training).

The results showed that major league athletes had a more controlled inflammatory response than younger athletes. When their blood cells were stimulated with the pathogen (LPS), both groups produced more interleukin 6, a cytokine that signals inflammation. However, the increase was more pronounced in young people. “The other important inflammatory cytokine, TNF-α, increased only in the younger group,” says the researcher.

Young athletes showed a more intense inflammatory response, while older athletes showed a more organized and controlled appearance. According to the researchers, this suggests that lifelong training can promote beneficial and balanced immune adaptation.

“Because they train regularly, their bodies are used to dealing with bouts of inflammation, which requires more intense stimuli to generate significant, long-term inflammatory responses. It is this type of ‘training’ that, over time, adapts the immune system, making it stronger.”

Minozzi points out that research on immune cells in athletes with long training histories has once again shown that decades of physical activity appear to “train” the regulation of inflammation. “The system does not stop responding, but it avoids exaggeration,” she concluded. “This is particularly interesting for a greater understanding of healthy aging, as disturbed inflammatory responses are linked to many chronic diseases.”