Inflammaging as a prodrome to Alzheimer's disease.

Recently, the term "inflammaging" was coined by Franceshci and colleagues to characterize a widely accepted paradigm that ageing is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses. Inflammaging differs significantly from the traditional five cardinal features of acute inflammation in that it is characterized by a relative decline in adaptive immunity and T-helper 2 responses and is associated with increased innate immunity by cells of the mononuclear phagocyte lineage. While the over-active innate immunity characteristic of inflammaging may remain subclinical in many elderly individuals, a portion of individuals (postulated to have a "high responder inflammatory genotype") may shift from a state of "normal" or "subclinical" inflammaging to one or more of a number of age-associated diseases. We and others have found that IFN-gamma and other pro-inflammatory cytokines interact with processing and production of Abeta peptide, the pathological hallmark feature of Alzheimer's disease (AD), suggesting that inflammaging may be a "prodrome" to AD. Although conditions of enhanced innate immune response with overproduction of pro-inflammatory proteins are associated with both healthy aging and AD, it is suggested that those who age "well" demonstrate anti-inflammaging mechanisms and biomarkers that likely counteract the adverse immune response of inflammaging. Thus, opposing the features of inflammaging may prevent or treat the symptoms of AD. In this review, we fully characterize the aging immune system. In addition, we explain how three novel treatments, (1) human umbilical cord blood cells (HUCBC), (2) flavanoids, and (3) Abeta vaccination oppose the forces of inflammaging and AD-like pathology in various mouse models.