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, 2019, 2324193
eCollection

Inflamm-Aging Is Associated With Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT Following LPS Stimulation

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Inflamm-Aging Is Associated With Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT Following LPS Stimulation

Aaron L Slusher et al. Mediators Inflamm.

Abstract

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p ≤ 0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p = 0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r = -0.404, p = 0.027; r = -0.427, p = 0.019; and r = -0.323, p = 0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p = 0.033) and negatively associated with telomere lengths (r = 0.353, p = 0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.

Conflict of interest statement

There are conflicts of interest to declare.

Figures

Figure 1
Figure 1
The associations of age with anthropometric characteristics in middle-aged and young adults. These data suggest that age, independent of weight gain or changes in BMI (a, b), is associated with the increased accumulation of centrally located visceral adiposity, identified by increased waist circumference, W : H ratio, body fat percentage, and sagittal diameter (c–f).
Figure 2
Figure 2
Plasma PTX3 and senescent-associated inflammatory cytokine concentrations. Plasma PTX3 concentrations were significantly lower in middle-aged compared to young adults (a). In addition, no differences in the proinflammatory cytokine IL-6 were observed (b), whereas plasma TNF-α concentrations were greater in middle-aged compared to young adults (c). Likewise, no differences in the anti-inflammatory cytokine IL-10 were observed (d), whereas plasma TGF-β concentrations were lower in middle-aged compared to young adults (e). ∗ indicates a significant difference in middle-aged compared to young adults (p ≤ 0.05).
Figure 3
Figure 3
Relative telomere lengths (T/S ratio) and the associations with age and body fat percentage. Telomere lengths measured from isolated PBMCs were significantly shorter in middle-aged compared to young adults (a). In addition, telomere lengths were negatively associated with increased age, body fat percentage, and circulating concentrations of the proinflammatory cytokine TNF-α (b–d). However, the relationship of telomere length with age and plasma TNF-α concentrations were no longer significant when after controlling for differences in body fat percentage. ∗ indicates a significant difference in middle-aged compared to young adults (p ≤ 0.05).
Figure 4
Figure 4
hTERT gene expression changes following 4-hour stimulation of isolated PBMCs with LPS and the associations with age and relative telomere length. hTERT gene expression was impaired in middle-aged and young adults following ex vivo stimulation of isolated PBMCs with LPS, PTX3, and PTX3+LPS (a). LPS-stimulated hTERT gene expression was negatively associated with age (b) and positively associated with relative telomere lengths (T/S ratio) (c). Likewise, the relationship between LPS-stimulated hTERT gene expression with age remained significant and tended toward a significant relationship with relative telomere length when controlling for differences in body fat percentage. ∗ indicates a significant difference in middle-aged compared to young adults; # indicates a significant difference compared to unstimulated control culture conditions (p ≤ 0.05).
Figure 5
Figure 5
Ex vivo production of LPS-stimulated PTX3 (a, b) and the senescent-associated inflammatory cytokines following 4- and 24-hour stimulation of isolated PBMCs with LPS, PTX3, and PTX3+LPS in middle-aged and young adults (c–j). In addition, the capacity of PTX3 to produce and alter the LPS-stimulated production of senescent-associated inflammatory cytokines ex vivo was examined. ∗ indicates a significant difference in middle-aged compared to young adults; # indicates a significant difference compared to unstimulated control culture conditions; ¥ indicates a significant difference compared to LPS-stimulated culture conditions; § indicates a significant difference compared to PTX3-stimulated culture conditions (p ≤ 0.05).

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