Effect of aging on neutrophil function in humans

One of the hallmarks of aging is chronic inflammation or "inflammaging", characterized by an increase in pro-inflammatory biomarkers observed during aging. Furthermore, immune responsiveness to stimulation is often defective. Neutrophils are the most abundant immune cell type in the circulation, acting as an early responder to infections. We performed an exploratory study to determine the effect of aging on neutrophil function. Participants in this study belonged to three age groups: young adults (20-30 y.o.), older adults (55-65 y.o.), and octo/nonagenarians (> 85 y.o.). Flow cytometry was performed to determine neutrophil subsets and baseline activation in the circulation. Neutrophils of older adults and octo/nonagenarians had an increased expression of CD66b compared to young adults. Neutrophil functions such as phagocytosis and NETosis were not affected by aging. Interestingly, ROS production at baseline was increased in older adults compared to young adults and octo/nonagenarians. Furthermore, PMA stimulation assays showed an increased IL-8 expression in older adults and octo/nonagenarians. Using RNA-sequencing, we report an increased expression of LTRs and LINE retrotransposons in neutrophils of old individuals. This was accompanied by an increased expression of interferon response genes: OAS2, IFIT1, and MX1, in older adults and octo/nonagenarians. In conclusion, we observed a more inflammatory profile of neutrophils in the elderly that is associated with interferon pathway activation and chemokine release, potentially induced by reactivation of transposable DNA elements.