Neutrophils in aging and aging‐related pathologies

Abstract

Over the past millennia, life expectancy has drastically increased. While a mere 25 years during Bronze and Iron ages, life expectancy in many European countries and in Japan is currently above 80 years. Such an increase in life expectancy is a result of improved diet, life style, and medical care. Yet, increased life span and aging also represent the most important non-modifiable risk factors for several pathologies including cardiovascular disease, neurodegenerative diseases, and cancer. In recent years, neutrophils have been implicated in all of these pathologies. Hence, this review provides an overview of how aging impacts neutrophil production and function and conversely how neutrophils drive aging-associated pathologies. Finally, we provide a perspective on how processes of neutrophil-driven pathologies in the context of aging can be targeted therapeutically.

Aberrant neutrophil degranulation in hospitalized patients with COVID‐19 partially remains for 6 months

“…In contrast, Spijkerman et al [24] report no signs of increased activation in the neutrophil compartment directly measured in peripheral blood of COVID-19 patients upon hospital admission versus healthy controls. However, the lack of mild patients and age-matched controls could perhaps explain why no differences were found, as aging affects neutrophil function [39]. Their analysis method was applied given that neutrophils get easily activated ex vivo when present for a prolonged period (>30 min) in a blood collection tube [40].…”

Neutrophils and their friends

“…Van Avondt et al 21 explore the process of immunosenescence, the muting of the immune system by the accumulated consequences of unresolved chronic inflammatory processes accumulated during aging. Like other elements of the immune system, neutrophils incur changes as hosts age, culminating in diminished functional capacity and untoward clinical outcomes for the elderly.…”

“…provide a comprehensive and thoughtprovoking overview of how the extraordinary versatility of neutrophils influences the behavior of other cells in the vessel wall and contributes to the initiation, maintenance, or both of inflammatory diseases in small, medium, or large vessels. The remarkable functional repertoire of neutrophils enables them to adapt to situations and modulate proinflammatory cells to suppress responses, drive fibrosis, promote thrombosis, or influence local vascular biology in other ways.Van Avondt et al21 explore the process of immunosenescence, the muting of the immune system by the accumulated consequences of unresolved chronic inflammatory processes accumulated during aging. Like other elements of the immune system, neutrophils incur changes as hosts age, culminating in diminished functional capacity and untoward clinical outcomes for the elderly.…”

Neutrophil dynamics and inflammaging in acute ischemic stroke: A transcriptomic review

“…Thus, the genomic link between inflammaging and neutrophils and strategies to reverse neutrophil immunosenescence in the elderly population requires further investigation (Simmons et al, 2021). Despite changes in receptor expression with aging (decreased CXCR4 expression as described below), circulating neutrophil counts remain stable in individuals without co-morbidities (Chatta et al, 1994;Van Avondt et al, 2022). Their production is not diminished (Corberand et al, 1986;Perez-de-Puig et al, 2015), rather, their functions and signaling pathways are impaired (Hazeldine et al, 2014;Sapey et al, 2014;Tseng and Liu, 2014;Simmons et al, 2021).…”

“…Biological variables such as age, sex, and comorbidities that profoundly affect the clinical outcome are often unaccounted for (Bosetti et al, 2017;McBride and Zhang, 2017). The complex factors underlying worsened outcomes in older individuals remain poorly defined, particularly in females, who are often underrepresented in research studies (van der Worp et al, 2005;Sohrabji et al, 2017;Tsivgoulis et al, 2017;Carcel et al, 2019). Older animals also have higher mortality and more severe neurological deficits, making them more challenging in research studies (Rosen et al, 2005;DiNapoli et al, 2008).…”