The complex role of neutrophils in healthy aging, inflammaging, and frailty.

Immune function alters as we age, and is often accompanied by chronic, low-grade inflammation termed "inflammaging." This leads cells to develop a senescence-associated secretory phenotype and release a range of proinflammatory cytokines and proteolytic enzymes. In individuals with frailty, inflammaging and senescence-associated secretory phenotype are increased, further reducing immune function and making individuals more susceptible to serious outcomes from infection. In this review, we focus on the role of neutrophils in healthy aging, inflammaging, and frailty. We summarize the key functions of neutrophils in an effective immune response to pathogens as well as discuss the important role of neutrophils in tissue repair and wound healing. We also discuss the decline in neutrophil immune responses associated with biological aging, in healthy older age and in individuals with frailty. We summarize the key role of metabolism and the antioxidant response in inflammatory neutrophil activation and identify the potential of therapeutics directed at longevity, metabolism, and cytokine signaling for the treatment of inflammaging.