New findings link long-term endurance training to a tougher, more adaptable immune system
Regular physical activity is known to strengthen muscles, lungs, and heart. Now, a growing body of research suggests that decades of endurance exercise may also prime the immune system, particularly natural killer (NK) cells, to respond more effectively to inflammatory challenges. In a study led by researchers from Brazil and Europe and published in Scientific Reports, older adults with a long history of endurance training exhibited NK cells that were more adaptable, less inflammatory, and metabolically efficient compared with their untrained peers.
What NK cells do and why they matter
Natural killer cells are frontline defenders in the immune system. They patrol for virally infected cells and malignant cells, and their performance can influence how the body handles infections and inflammatory stress. The study focused on nine older adults (average age around 64), split into two groups: those with endurance training histories and those without. The researchers examined the phenotype, function, and mitochondrial metabolism of NK cells, both at rest and after inflammatory stimuli.
Endurance training and healthier immunometabolism
Compared with non-athletes of the same age, the endurance-trained group showed fewer inflammatory markers and more anti-inflammatory signals in their NK cells. This suggests better control of inflammation, which is important because chronic, low-grade inflammation is linked to aging and a range of diseases. The trained participants also demonstrated more efficient energy use within NK cells, implying improved immunometabolism — the way immune cells manage energy to respond to threats.
Mechanisms behind the enhanced NK cell function
To understand why endurance training shapes NK cells, researchers exposed NK cells from both groups to different pharmacological blockers. Propranolol, which dampens adrenergic signaling, and rapamycin, which inhibits the mTORC1 pathway, were used to tease apart signaling routes that drive NK cell activity. Even with these pathway blocks, NK cells from trained older adults maintained immune function, whereas those from untrained peers showed signs of exhaustion or a faltering inflammatory response. These results point to two key ideas: long-term endurance training cultivates resilient immunometabolic adaptations, and it helps NK cells become more mature and better prepared to handle stressors without overreacting.
A broader view: master athletes and aging immune responses
In a related comparison, researchers looked at younger and master athletes (older athletes with more than 20 years of training) who underwent an acute exercise session. Master athletes displayed a more controlled inflammatory response than younger athletes after stimulation with a pathogen surrogate. While both groups increased IL-6, a marker of inflammation, the rise was greater in the younger cohort. TNF-α increased only in the younger group. This pattern suggests that lifelong training promotes balanced immune adaptation, potentially contributing to healthier aging by preventing exaggerated inflammatory responses.
Implications for aging and public health
These findings align with the idea that lifestyle factors such as sleep, nutrition, vaccination, and stress management, in addition to physical activity, shape immune health. Regular endurance exercise appears to modulate inflammatory responses over time, reduce cellular exhaustion, and optimize energy sensing in NK cells. Researchers emphasize that exercise is one modifiable factor that can support a robust immune system as we age, potentially lowering the risk of inflammatory-related diseases.
What this means for readers
For older adults and those planning healthy aging strategies, the message is clear: sustained endurance activity — even past middle age — may recalibrate immune function in meaningful ways. The study’s lead investigators note that decades of training help the immune system respond to challenges without tipping into excessive inflammation, a balance that could contribute to longer, healthier lives.
About the study and future directions
The study, supported by FAPESP and conducted by Brazilian and international researchers, analyzed NK cells’ flexibility and metabolic state in older adults with vs. without endurance training. The team plans further work to explore how other lifestyle factors interact with exercise to influence immune aging, with the ultimate goal of guiding evidence-based exercise recommendations for immune health across the lifespan.
