Natural Killer Cell Dysfunction in the Aging of the Immune System
The immune system is a highly complex collection of many different types of specialized cells. As is usually the case in scientific research, some areas receive more attention than others, particularly in the context of aging, wherein funding is limited and there are fewer researchers focus on the topic. Of late natural killer cells have received more attention as a result of their role in clearance of senescent cells. Given that the research community has built the case that senescent cell accumulation is actually quite important in aging, finding out how and why the immune system fails to clear these cells in an aged tissue environment has become more of a pressing question.
Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer's and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease.
One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging ("inflammaging").
NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.