Longevity Briefs: Endurance Training Is Linked To More Flexible Immune Cells In Old Age

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The immune system naturally declines with age, making us more susceptible to infections and diseases. The ageing of the immune system also results in ‘inflammaging’, a state of chronic low-level inflammation that contributes to many age-related diseases. We know that exercise can counteract immune ageing to a certain extent, contributing to its ability to delay age-related disease. Yet we know surprisingly little about how exactly exercise achieves its many health benefits at the cellular and molecular level.

In this study, researchers focus in on a type of white blood cell called a natural killer (NK) cell. NK cells are part of the first line of defence against infection. This is because unlike the more widely known T and B cells, NK cells are able to recognise and attack pathogens without ever having contacted them before, buying time for said T and B cells to mount their immune responses.

The discovery:

In the study, researchers recruited a small group of healthy older men: 5 endurance-trained participants (average age 63.6) and 4 untrained participants (average age 64.3). The endurance-trained individuals had a history of competitive sport or structured training, were still actively engaged in said sport or training, and had a higher peak oxygen uptake (VO2peak).

The researchers isolated NK cells from the participants, cultured them in a lab for 14 days, and exposed them to one of two drugs: propranolol, a drug that blocks the effects of stress hormones like adrenaline (NK cells are activated by stress, so this has the effect of suppressing NK cell activity); or rapamycin, a drug that interferes with a key cellular growth and metabolism pathway called the mTOR pathway (this mimics the effects of low nutrient availability). These drugs were each tested with or without an additional inflammatory stimulus.

The researchers found that the NK cells of trained participants adapted better to these conditions than the cells of untrained participants. The NK cells of the trained participants had increased markers of maturity and cytotoxicity (their ability to kill infected cells) after exposure to high doses of propranolol when compared to those of untrained participants. They also showed fewer markers of cellular senescence (when cells reach their replication limit and are unable to divide further). When it came to rapamycin, the researchers found that higher doses of this drug decreased markers of NK cell activity in both groups. However, in the presence of an inflammatory stimulus, the NK cells from the trained participants appeared more resistant to the effects of high dose rapamycin when compared to the untrained group.

The implications:

These findings suggest that the NK cells of the endurance trained individuals were more metabolically flexible than those from their untrained counterparts. That is to say that when faced with an inflammatory stimulus, their NK cells appeared to be better able to maintain their function in spite of drug-induced metabolic and hormonal disruptions. This could help explain why exercise appears to preserve NK function in old age, in the face of age-related metabolic dysfunction.

This study had a small sample size and was observational in nature, meaning that the differences in NK cell function might not have been entirely due to exercise, but rather due to other lifestyle practices (people who exercise a lot are generally more likely to look after their health in other ways). However, other studies have demonstrated that repeated exposure to adrenaline during exercise, combined with adequate rest, directly enhances NK cell function. It’s a safe bet to think that exercise probably contributed to the ‘metabolic flexibility’ observed in this study, adding to the many reasons why remaining physically active into old age is a good idea.