A new study reveals that decades of endurance exercise, such as running and cycling, may keep the immune system youthful and resilient in older adults. Researchers found that natural killer cells in trained individuals functioned better, showed lower inflammation, and resisted fatigue under stress. The findings suggest physical activity trains the immune system much like it does muscles.
An international team of scientists, led by researchers from São Paulo State University (UNESP) in Brazil and Justus Liebig University Giessen (JLU) in Germany, examined the immune cells of older adults with a long history of endurance training. The study, funded by FAPESP and published in Scientific Reports in 2025, focused on natural killer (NK) cells, which target infected or damaged cells including viruses and cancer.
The researchers analyzed samples from nine participants with an average age of 64, divided into trained and untrained groups. The trained group consisted of individuals who had engaged in endurance exercises like long-distance running, cycling, swimming, rowing, and walking for more than 20 years. "In these individuals, NK cells functioned better in the face of an inflammatory challenge, in addition to using energy more efficiently. Therefore, it's as if exercise also trains the immune system," says Luciele Minuzzi, a visiting researcher at JLU.
Compared to non-athletes, the trained older adults had fewer inflammatory markers and more anti-inflammatory markers, indicating better control of inflammation. Experiments exposed NK cells to pharmacological agents like propranolol, which blocks the adrenergic pathway, and rapamycin, which inhibits the mTORC1 signaling pathway. Even under these conditions, NK cells from trained individuals maintained function, while those from untrained ones showed exhaustion.
"Trained older individuals demonstrate more efficient and adaptable immunity, with greater metabolic control and less propensity for cellular exhaustion," Minuzzi explains. A related analysis compared 12 master athletes (average age 52, over 20 years of training) with young athletes (average age 22, over 4 years of training). Master athletes exhibited a more controlled inflammatory response to pathogens, producing less IL-6 and no increase in TNF-α, unlike the younger group.
Fábio Lira, project coordinator at UNESP's Presidente Prudente campus, notes that lifelong training adapts the immune system to handle inflammation without exaggeration, potentially aiding healthy aging. The immune system is influenced by factors like sleep, nutrition, and stress, but consistent exercise emerges as a key modulator.