Inflammation and neutrophil immunosenescence in health and disease: Targeted treatments to improve clinical outcomes in the elderly

Despite increasing longevity, many old people are not in good health. There has been an increase in the prevalence of age-associated multi-morbidity (two or more chronic conditions in the same person). Also, severe infections, such as pneumonia, remain significant causes of mortality and morbidity in this aging group. Many chronic health conditions share risk factors such as increasing age, smoking, a sedentary life style and being part of a lower socioeconomic group. However, despite this, multi-morbidities often co-occur more commonly than would be predicted. This has led to the hypothesis that they share common underlying mechanisms. This is an important concept, for if it were true, treatments could be devised which target these common pathways and improve a number of age-associated health conditions. Many chronic illnesses associated with multi-morbidity and severe infections are characterized by an abnormal and sustained inflammatory response, with neutrophils being key effector cells in the pathological process. Studies have described aberrant neutrophil functions across these conditions, and some have highlighted potential mechanisms for altered cell behaviours which appear shared across disease states. It has been suggested that altered functions may represent neutrophil "senescence". This review considers how and why neutrophil functions change as the cell ages, and how and why neutrophil functions change as the host ages in health and disease and discusses whether neutrophil functions could be targeted to improve health outcomes in older adults.