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In recent years, multiple studies of older adults have identified strong relationships between serum markers of inflammation and frailty, worsening chronic disease, disability, and mortality. Although these studies are not proof that the chronic activation of inflammatory pathways causes these adverse health care outcomes, recent biological evidence supports that chronic exposure to inflammatory mediators leads to alterations in multiple physiological systems. These in turn contribute to the older adult's vulnerability to adverse health outcomes. Because the activation of inflammatory pathways appear to be so intricately linked to many aging systems, some investigators have propagated use of the term “inflammaging” as a summary of the physiological and molecular changes consistent with the aging process that are known to be associated with chronic activation of inflammatory pathways. Other investigators now utilize “chronic inflammation” as a descriptor for the ongoing activation of the innate immune system that has been observed in some older individuals. The rising use of these terms in aging research and in clinical practice signifies the emerging importance of inflammation as an important contribution, adverse health outcomes in older adults. The study of the clinical utility of relevant inflammatory biomarkers, the understanding of the specific age-related mechanisms that activate and sustain chronic inflammation in older adults, and exploration of the impact that inflammatory mediators and pathway activation have on specific physiological systems and on the overall vulnerability observed in older adults are certain to impact both research and clinical agendas for older adults in the coming years. Given this crucial focus and the importance of understanding this emerging area of investigation for those who care for older adults, and the high likelihood that both investigators and clinicians will likely encounter this important and evolving area of aging research in the coming years, this chapter will (1) describe evolving definitions of inflammation used in the context of aging research and clinical practice, (2) provide a review of the robust relationships between activation of inflammatory pathways and adverse health outcomes previously identified in older adults, (3) describe the pertinent areas of the molecular biology of inflammation necessary to understand how and why older adults are more vulnerable to inflammatory pathway activation, (4) characterize the relationships between inflammatory pathway activation, multisystem decline, and the biological vulnerability observed in older adults, and (5) highlight the current and potential future clinical relevance of inflammation in older adults.

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Inflammation, often referred to as the activation of the innate immune system, is a complex and important physiological response to external threats. In general, it is a critical housekeeping function that acts to fight acute infections and repair wounds through common biological pathways that in turn activate hormonal, thrombotic, and cytokine pathways (Figure 4-1). These pathways function throughout the life span to attenuate or eliminate countless infections and injuries from becoming life-threatening events. This inflammatory signaling is in general a self-limiting process that ends when the infection or injury is resolved and the local and systemic inflammatory pathways return to ...

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