Introduction to Ageing of the Innate Immune System
Over the past century, human life expectancy has doubled in developed countries and is continuing to increase at a rate of 2 years per decade. However, although life expectancy has increased, advanced age is accompanied by an increase in susceptibility to
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Introduction to Ageing of the Innate Immune System Niharika A. Duggal and Janet M. Lord
1.1
Introduction
Over the past century, human life expectancy has doubled in developed countries and is continuing to increase at a rate of 2 years per decade. However, although life expectancy has increased, advanced age is accompanied by an increase in susceptibility towards infection and development of chronic illnesses that have a negative impact on an individual’s quality of life. Even adults considered to have undergone healthy ageing show a significant decline in immune competence, termed immunosenescence, which is responsible for the increased rate of infections with advancing age (DiCarlo et al. 2009). Recent studies have also reported a reduced ability to mount a robust immune response to vaccination, combat new pathogens or maintain immunity to persistent infections such as Herpes zoster in older adults (Gavazzi and Krause 2002b; Trzonkowski et al. 2009; Weinberger et al. 2008). Delaying or reversing the effects of ageing on the immune system may therefore be extremely beneficial to the health and quality of life of the elderly population (Dorshkind et al. 2009).
1.2
Inflammaging
A universal feature of physiological ageing is a higher basal production of proinflammatory cytokines (IL-1β, IL-6, IL8, TNFα and IL-15), accompanied by a reduced production of anti-inflammatory cytokines (IL-10) known as ‘Inflammaging’ (Franceschi et al. 2007). Importantly, inflammaging is a predictor of frailty and mortality in aged humans. Studies in centenarians (Di Bona et al. 2009) and extremely long-lived mice (Arranz et al. 2010) show that long-lived individuals maintain the cytokine profile of younger adults. In addition to increased cytokines, other inflammatory markers including C-reactive protein (CRP) and clotting factors (fibrinogen) J. M. Lord () · N. A. Duggal MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK e-mail: [email protected]
J. A. Bosch et al. (eds.), Immunosenescence, DOI 10.1007/978-1-4614-4776-4_1, © Springer Science+Business Media New York 2013
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N. A. Duggal and J. M. Lord
are also increased with age. The underlying mechanisms driving inflammaging are thought to be varied (Krabbe et al. 2004) and include: the increase in adipose tissue which is a significant source of inflammatory cytokines and pro-inflammatory hormones termed adipokines (Fantuzzi 2005); decreased production of sex steroids many of which are anti-inflammatory (Nilsson 2007); sub-clinical infections (Effros 2001); a sedentary lifestyle (Lavoie et al. 2010) and constitutive low-level production of cytokines by monocytes (discussed below). The rest of this chapter will focus upon the age-related changes to the functioning of the cells of the innate immune system as it is these changes that dramatically affect the ability to combat bacterial and viral infections in old age.
1.3 Age-Related Changes to Innate Immune Cell Production The innate immune system
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