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. 2018 Feb 9;9:169. doi: 10.3389/fimmu.2018.00169

Figure 4.

Figure 4

Age-associated changes in adipose tissue macrophages and immunometabolic health in humans (A) and mice (B). This schematic is a theoretical representation based on the limited empirical evidence that is available. With advancing age in humans (A), subcutaneous adipose tissue macrophage content increases steadily until 31–33 years whereupon numbers slightly decline, until 45 years old (174). Although absolute adipose tissue macrophage content declines from around the age 31–33 years old until 45 years old, at least, the presence of more pro-inflammatory activated macrophages [M1-like/intermediate, or “double-negative” (CD11c−CD206−) macrophages] increases, which is associated with a decline in insulin sensitivity. With advancing age, insulin sensitivity continues to decline, while low-grade systemic inflammation begins to steadily increase from middle age into old age. With advancing age in mice (B), an increase in pro-inflammatory macrophages within visceral adipose tissue that produce TNF-α and IL-6 and have downregulated PPAR-γ expression is also observed up to 18–24 months, at least (51, 170). Further, in middle-aged mice (44 weeks old), “double-negative” (CD11c−CD206−) and M2-like macrophages are largely unchanged or are modestly elevated, while M1-like macrophages exhibit a slight decline (172). Therefore, it is theorised that there is a continued pro-inflammatory macrophage activation/polarisation with advancing age in humans, independent of changes in absolute counts within the adipose tissue. Further, the same pattern of events appears to occur within murine adipose tissue, although the age at which this shift to a pro-inflammatory bias occurs is unknown. The similarities between data from aged mice and humans indicate that macrophages adopt a predominantly pro-inflammatory M1-like/intermediate, or “double-negative” (CD11c−CD206−) phenotype into old age, contributing to the increased systemic inflammation and impaired metabolic health exhibited by older individuals. Abbreviations: CD, cluster of differentiation marker; IL, interleukin; PAI-1, plasminogen activator inhibitor 1; PPAR-γ, peroxisome proliferator-activated receptor gamma; TNF-α, tumour necrosis factor-α.