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Review
. 2015 Dec;98(6):937-43.
doi: 10.1189/jlb.5MR0315-104R. Epub 2015 Jul 17.

Paradoxical changes in innate immunity in aging: recent progress and new directions

Ruth R Montgomery  1 , Albert C Shaw  2
Affiliations
Review

Paradoxical changes in innate immunity in aging: recent progress and new directions

Ruth R Montgomery et al. J Leukoc Biol. 2015 Dec.

Abstract

Immunosenescence, describing alterations, including decline of immune responses with age, is comprised of inappropriate elevations, decreases, and dysregulated immune responses, leading to more severe consequences of bacterial and viral infections and reduced responses to vaccination. In adaptive immunity, these changes include increased proportions of antigen-experienced B and T cells at the cost of naïve cell populations. Innate immune changes in aging are complex in spanning multiple cell types, activation states, and tissue context. Innate immune responses are dampened in aging, yet there is also a paradoxical increase in certain signaling pathways and cytokine levels. Here, we review recent progress and highlight novel directions for expected advances that can lead the aging field to a new era of discovery that will embrace the complexity of aging in human populations.

Keywords: Toll-like receptor; dendritic cell; immunosenescence; polymorphonuclear leukocyte; systems immunology.

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Figures

Figure 1.
Figure 1.. Effects of aging on innate immune cells.
In aging, innate immune cells show altered responses and up-regulated and down-regulated functions. DC-SIGN, DC-specific ICAM-3-grabbing nonintegrin; STAT1-P, phosphorylated STAT1; Flg-conj, flagellin-conjugated.
Figure 2.
Figure 2.. Systems investigation of effects of aging.
Schematic view of systems investigation integrating multiple components of immune function. Collection of blood or tissue samples from enrolled subjects (older and younger) can be assessed for multiple assays, including DNA polymorphisms and genotyping; phenotyping of surface receptor expression; signaling pathway activity; and ligand-stimulated responses, which may be correlated with clinical parameters of study subjects for a more comprehensive view of immune status. Computational models can be tested and refined in a validation cohort. GWAS, genome-wide association studies; SNP, single nucleotide polymorphism; RNA-seq, RNA sequencing.
See this image and copyright information in PMC

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