Beyond strengthening muscles, lungs, and the heart, regular physical activity also fortifies the immune system. This conclusion comes from a study of older adults who had a long history of endurance training—activities such as long‑distance running, cycling, swimming, rowing, and walking.
The international research team examined the defense cells of these individuals and discovered that their “natural killer” cells, which patrol the body to eliminate viruses and damaged cells, were more adaptable, less inflamed, and metabolically more efficient.
The work, published in the journal Scientific Reports, focused on natural killer (NK) cells, a white‑blood‑cell type that can destroy infected, diseased, and even cancerous cells. NK cells are on the front lines of immunity because they recognize and attack viral and other pathogens. Researchers studied the NK cells of nine participants, whose average age was 64, and divided them into untrained and endurance‑trained groups.
“In a prior study we showed that obesity and a sedentary lifestyle can accelerate the aging of defense cells. We wanted to explore the opposite: whether older adults who have practiced endurance exercise for more than 20 years possess a better‑prepared immune system. And that’s what we found.”
“In these individuals, NK cells responded more effectively to inflammatory challenges while also using energy more efficiently. It’s as if exercise also trains the immune system,” explained Luciele Minuzzi, a visiting scholar at Justus‑Liebig University Giessen in Germany.
The investigation was part of Minuzzi’s postdoctoral work and belongs to a larger project led by researchers from São Paulo State University (UNESP) in Brazil.
According to the study, sustained endurance training modulates the inflammatory response over time.
“When we compared the cells of trained older adults with those of age‑matched non‑athletes, we found that the former showed fewer inflammatory markers and more anti‑inflammatory markers. This indicates a superior control of inflammation compared with non‑athletic peers,” said Professor Fábio Lira, coordinator of the project at UNESP’s Faculty of Science and Technology.
Lira noted that many factors influence the immune system—including sleep quality, diet, vaccination status, stress, sedentary habits, and immunosuppressive drugs—which can diminish defense‑cell activity. “Physical exercise is one factor that can strengthen immunity, and this project explores how it modulates the immune response over time,” he added.
In addition to assessing phenotype, function, and mitochondrial metabolism of NK cells responding to inflammatory stimuli, the team exposed expanded NK cells from trained and untrained older adults to pharmacological blockers such as propranolol and rapamycin.
“Trained older individuals display more efficient, adaptable immunity with better metabolic control and less tendency toward cellular exhaustion. Regular exercise appears to positively affect both adrenergic sensitivity and cellular energy sensors, leading to a more balanced, less inflammatory response to external stimuli,” Minuzzi reported.
Propranolol blocks the adrenergic pathway—neural and endocrine signals released by adrenaline and noradrenaline—allowing isolation of this activation in NK cells. Rapamycin inhibits the mTORC1 signaling pathway, which regulates cell growth and proliferation. In the study, rapamycin altered NK‑cell phenotype and reduced their in‑vitro expansion at high doses (100 ng/mL).
“With the signaling pathways blocked, NK cells from trained older adults maintained immune function, whereas those from untrained participants showed exhaustion or failure during inflammatory responses. Thus, long‑term endurance training is associated with protective “immunometabolic” adaptations in NK cells in older adults,” Minuzzi explained.
In other words, the cells mature, become less senescent, and are better prepared metabolically to meet inflammatory or pharmacological stressors,” she added.
A recent study, also published in Frontiers in Immunology, compared the immune response of young and master athletes before and after an acute exercise session. Researchers analyzed whole blood and PBMC data from 12 master athletes (average age 52 with over 20 years of continuous training) and contrasted them with data from young athletes (average age 22, at least four years of training).
The results showed that master athletes had a more controlled inflammatory response than younger participants. When stimulated with LPS, both groups produced more IL‑6, an inflammation‑signaling cytokine, but the increase was greater in the younger group. TNF‑α rose only in the younger athletes.
The younger athletes exhibited a sharper inflammatory reaction, while the older athletes demonstrated a more regulated profile. The researchers suggest that lifelong training can promote beneficial, balanced immune adaptation.
“Because they train regularly, their bodies are accustomed to managing inflammatory episodes, which require stronger stimuli to elicit significant long‑term responses. This form of “training” over time shapes the immune system, making it more robust,” Minuzzi stated.
Minuzzi emphasized that studies of athletes with extensive training histories consistently show that decades of physical activity seem to “train” the regulation of inflammation. “The system remains responsive but avoids over‑exuberance. This insight is crucial for understanding healthy aging, given the link between dysregulated inflammation and chronic disease,” she concluded.