Innate immunity and aging

Abstract

Advanced age is associated with defects in all of the cells of the innate immune system, including numbers, function, and early stages of activation. This review, presents the current state of the field on the impact of age on the innate immune system. The analysis of the literature suggests that a dysfunctional innate immune system is a contributing factor to aberrant outcomes after injury or infection and to the development of many of the diseases observed in the elderly. Gaining an understanding of the nature of the defects in innate immune cells may allow the development of therapeutic strategies aimed to restore innate immune function in aged individuals.

Introduction

Aging is associated with a decline in health, partially attributed to defects in immunity [reviewed in Katz et al., 2004]. The complex process of immunosenescence affects both the innate and the adaptive arms of the immune system (Allman and Miller, 2005b, Gomez et al., 2005, Weng, 2006). Commonly observed in the elderly are decreased T cell memory, exhaustion of the naïve T cell population with involution of the thymus (Weng, 2006), decline in B cell production reflected in defective humoral immunity (Allman and Miller, 2005a, Riley et al., 2005), and a chronic inflammatory state referred to as, “inflamm-aging” (Franceschi et al., 2000). As a result, older subjects are less able to mount an immune response following an infectious challenge than are young adults (Linton and Dorshkind, 2004) and more susceptible than young to viral and bacterial infections, opportunistic infections, reactivation of latent viruses, autoimmune diseases, and neoplasias (Effros, 2003, Murasko and Jiang, 2005, Pawelec et al., 2005, Prelog, 2006).

Cumulative evidence indicates that aging exerts significant effects on all cells of the innate immune system (Agrawal et al., 2008, Gomez et al., 2005, Plackett et al., 2004, Plowden et al., 2004a, Sebastian et al., 2005, Solana et al., 2006). Impairment of multiple neutrophil functions, such as phagocytic capacity, synthesis of reactive oxygen intermediates, and intracellular killing efficiency is observed in the elderly (Fulop et al., 2004, Tortorella et al., 2007). Advanced age also affects macrophage functions, including phagocytic activity, cytokine and chemokine secretion, antibacterial defense, infiltration and wound repair, and antigen presentation (Sebastian et al., 2005). There is contradictory evidence regarding the effects of aging on natural killer (NK) and natural killer T (NKT) cell numbers and functional properties (Mocchegiani et al., 2003, Peralbo et al., 2007). Although studies are limited, mast cell (Hart et al., 1999, Montagna and Carlisle, 1990, Nguyen et al., 2005) and eosinophil (Kasper et al., 1999, Leng et al., 2005, Yagi et al., 1997) numbers and functional properties have also shown age-related alterations. These latter findings are particularly interesting in the context of the age-associated increase in morbidity and mortality with asthma, autoimmune disorders and atherosclerosis. Thus, differences in both the number and function of multiple cell types, contribute to the defective innate immunity associated with advanced age. Moreover, new evidence has pointed to intracellular molecular pathways that lead to impaired activation of immune cells. We next review, in detail, the age-associated changes in number, function and cell signaling in cells of the innate immune system.