Innate immunity and aging (original) (raw)
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The innate immune system and aging: What is the contribution to immunosenescence?
Open Longevity Science, 2012
The immune system plays an important role in the defence against various threats to health, such as pathogens, cancer cells or modified-self proteins. With aging there is a decrease in the immune response, called immunosenescence, concomitantly with the increase in some age-related diseases such as infections, autoimmune disorders, chronic inflammatory diseases and cancer. The immune response is traditionally divided between innate and adaptive immune responses. Accumulating evidence suggests that immunosenescence is not only restricted to the adaptive but also affects the innate immune system. Assessment of innate immune system functions revealed that it is also susceptible to age-related dysregulation. Furthermore, it is becoming clear that the sustained function of innate cells is indispensable for the adequate functioning of the adaptive immune response. This review will describe the changes in the innate immune response with aging and the recent discoveries, which may shed new light on its contribution to immunosenescence.
Impact of aging on innate immunity
1998
Immune responses in higher organisms are triggered by the recognition of a limited diversity of microbiological products by cells of the innate or ''natural'' immune system. As a result, in addition to the direct protective effect of natural immunity, antigen-presenting cells, particularly dendritic cells, are activated to process and present an enormous number of peptide antigens to the T lymphocytes of the adaptive immune system. These, together with the B lymphocytes, then mediate specific immune responses and maintain acquired immunological memory. The aging immune system is less well able to cope with infectious disease than the youthful immune system; this review will briefly consider what is known of the age-associated alterations in innate immunity, and how these may also impact on adaptive immunity. J. Leukoc. Biol. 64: 703-712; 1998.
Signal Transduction of the Aging Innate Immune System
Current Immunology Reviews, 2007
Aging is associated with defects in the cells of the innate immune system, in both their function and number. During the last decade, new evidence has revealed impairment in the early stages of the activation processes that trigger innate immune cells. In this review, the impact of aging on signal transduction in macrophages (M s), as pivotal representatives of innate immunity, is presented. Emphasis is put on the classical intracellular pathways of M activation in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-). The critical analysis of the literature reveals that, when intracellular signaling defects occur, the ability of M s to respond appropriately is significantly compromised. Taken together, these observations may help explain why aged individuals have inflammatory and immune defects that range from decreased capacity to fight infections to delayed healing of dermal wounds. Gaining an understanding of the nature of the defects in innate immune cells, such as M s, may shed light on the development of therapeutic strategies aimed at restoring innate immune function in aged individuals so they can better combat infectious challenges.
Human innate immunosenescence: causes and consequences for immunity in old age
Trends in Immunology, 2009
The past decade has seen an explosion in research focusing on innate immunity. Through a wide range of mechanisms including phagocytosis, intracellular killing and activation of proinflammatory or antiviral cytokine production, the cells of the innate immune system initiate and support adaptive immunity. The effects of aging on innate immune responses remain incompletely understood, particularly in humans. Here we review advances in the study of human immunosenescence in the diverse cells of the innate immune system, including neutrophils, monocytes, macrophages, natural killer and natural killer T (NKT) cells and dendritic cells-with a focus on consequences for the response to infection or vaccination in old age.
Immunity, 2006
Adaptive immunity undergoes severe deterioration with age and represents the main problem in the elderly. However, evidence accumulated over the last decade supports the hypothesis that aging also has a profound impact on innate immunity, which in turn markedly impacts the health and longevity of older people.
Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors
Trends in Immunology, 2009
Aging affects every innate immune cell, including changes in cell numbers and function. Defects in the function of some cells are intrinsic, whereas for other cells, defects are extrinsic and possibly the consequence of the complex interactions with other cell types or the environmental milieu that is altered with aging. Abnormal function contributes to worsened outcomes after injury or infection and leads to diseases observed in the elderly. Knowing the mechanisms responsible for the aberrant function of innate immune cells might lead to the development of therapeutic strategies designed to improve innate immunity in aged individuals. Herein, advances in the field of innate immunity and aging with a focus on neutrophils, macrophages and dendritic cells in laboratory animals are discussed. inflammatorymediators that play a role in the chronic inflammatory state that is known as inflamm-aging' . As a result, older subjects have impaired immune responses after infectious challenges compared with young adults [6], rendering them more susceptible to viral and bacterial pathogens, opportunistic infections, reactivation of latent viruses, autoimmune diseases and neoplasias [7-10].