Immune Senescence, Immunosenescence and Aging

Abstract

With aging, there is increased dysfunction of both innate and adaptive immune responses, which contributes to impaired immune responses to pathogens and greater mortality and morbidity. This age-related immune dysfunction is defined in general as immunosenescence and includes an increase in the number of memory T cells, loss of ability to respond to antigen and a lingering level of low-grade inflammation. However, certain features of immunosenescence are similar to cellular senescence, which is defined as the irreversible loss of proliferation in response to damage and stress. Importantly, senescence cells can develop an inflammatory senescence-associated secretory phenotype (SASP), that also drives non-autonomous cellular senescence and immune dysfunction. Interestingly, viral infection can increase the extent of immune senescence both directly and indirectly, leading to increased immune dysfunction and inflammation, especially in the elderly. This review focuses on age-related immune dysfunction, cellular senescence and the impaired immune response to pathogens.

Keywords: aging; immunity; immunosenescence; senescence; senolytic.

FIGURE 1

Innate and adaptive immune system dysfunction with aging and infection. With aging, both innate and adaptive immunity show dysregulated responses against infection, resulting in suboptimal anti-pathogenic responses and increased inflammation. The reduced Type I IFN secretion and functional defects in innate immune cells including senescence results in inefficient clearance of pathogens. Defects in DC trafficking and T cell priming also cause impaired adaptive immune response including antibody generation and cellular T cell responses. Instead, infiltration of inflammatory senescent immune cells is increased, which induces tissue damage.