Innate immunity is the first line of defence against invading microorganisms. With advancing age there is a chronic deterioration of immune function, termed immunesenescence, leading to increased susceptibility to infection. Neutrophils are the most abundant leukocyte in blood and the first immune cell to arrive at sites of bacterial infection, making them critical intermediaries in the effective resolution of infection.
We show for the first time that a 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people…..Neutrophil migration is a key component for the resolution of infection and control of inflammation.
Neutrophil migration is a key component for the resolution of infection and control of inflammation. Along with age-associated reductions in bacterial clearance, migratory dysfunction can lead to increased morbidity and mortality from bacterial infections (Liang and Mackowiak, 2007). Defective migration results in poor resolution of inflammation and wound repair in aged mice (Brubaker et al., 2013). Additionally, if the neutrophil does not migrate accurately between tissues, collateral damage is augmented by elevated proteinase release from the cell, enhancing the inflammatory milieu and potentially contributing to the increased infection associated frailty (Liou and Campbell, 1996, Pham, 2006 and Fleming and Elliot, 2005). Recent work from our group showed that neutrophils from older adults migrated with a similar speed but reduced velocity and accuracy when compared to younger participants (Sapey et al., 2013). Our findings here show that velocity and accuracy were similarly reduced in our older cohort compared to young subjects, but we now add that the reduced habitual activity of our elders is associated with this loss of migratory accuracy.
These data suggest that efficient neutrophil migration is not only improved by physical exercise but is highly plastic and fundamentally dependent on it. In support of a physical activity effect on neutrophil function, we show that just a 2-fold difference in habitual physical activity levels was sufficient to be associated with increased neutrophil chemotaxis and chemotactic index. Moreover, none of our participants were actively engaged in structured exercise training as stated in their IPAQ’s, thus higher habitual physical activity levels resulted in significantly better migration.
Regular physical activity is known to positively alter the metabolism of individuals and reduce the risk for type-2 diabetes and associated cardiovascular disorders (Gleeson et al., 2011). Indeed, we observed a significantly lower measure of insulin resistance and diabetes risk (HOMA-IR) in the MA group (p=0.004). Lower circulating insulin and fasting glucose levels coupled with reduced body fat and adipocyte related inflammation are a common feature of physically active individuals. Additionally, insulin signals through the PI3K/AKT pathway also and may account for altered PI3K activation in the elderly with increased circulating insulin concentrations ( Schulman et al., 2007). Recently neutrophils were shown to facilitate insulin resistance in obese mice, highlighting a specific connection between innate immune function and metabolism