Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function

Abstract

Summary Chronic inflammation in older individuals is thought to contribute to inflammatory, age‐related diseases. Human monocytes are comprised of three subsets (classical, intermediate and nonclassical subsets), and despite being critical regulators of inflammation, the effect of age on the functionality of monocyte subsets remains to be fully defined. In a cross‐sectional study involving 91 healthy male (aged 20–84 years, median 52.4) and 55 female (aged 20–82 years, median 48.3) individuals, we found age was associated with an increased proportion of intermediate and nonclassical monocytes (P = 0.002 and 0.04, respectively) and altered phenotype of specific monocyte subsets (e.g. increased expression of CD11b and decreased expression of CD38, CD62L and CD115). Plasma levels of the innate immune activation markers CXCL10, neopterin (P < 0.001 for both) and sCD163 (P = 0.003) were significantly increased with age. Whilst similar age‐related changes were observed in both sexes, monocytes from women were phenotypically different to men [e.g. lower proportion of nonclassical monocytes (P = 0.002) and higher CD115 and CD62L but lower CD38 expression] and women exhibited higher levels of CXCL10 (P = 0.012) and sCD163 (P < 0.001) but lower sCD14 levels (P < 0.001). Monocytes from older individuals exhibit impaired phagocytosis (P < 0.05) but contain shortened telomeres (P < 0.001) and significantly higher intracellular levels of TNF both at baseline and following TLR4 stimulation (P < 0.05 for both), suggesting a dysregulation of monocyte function in the aged. These data show that aging is associated with chronic innate immune activation and significant changes in monocyte function, which may have implications for the development of age‐related diseases.

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

“…Our data do not address the potential impact of age and gender on monocyte apoptosis (14,73,74). Both HIV Ϫ and HIV ϩ groups represent similar gender (no more than 25% female) and age distributions, but our cohort is limited in the representation of females and aged individuals (see Table S1 in the supplemental material).…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…29,[53][54][55][56] This "activated pattern" is confirmed by the expansion of CD11b expression and by the reduction of CD38, CD62L, and CD115 expression. Plasma levels of soluble CD163 (sCD163) and CXCL10, markers of innate immune activation, increase with age.…”

“…Plasma levels of soluble CD163 (sCD163) and CXCL10, markers of innate immune activation, increase with age. 54 Interestingly, also basal levels of IL-10, an anti-inflammatory cytokine, are higher in older than in younger individuals. 29 Van Duin et colleagues registered a reduced production of IL6 and TNF-a following TLR-1/2 stimulation.…”

Role of CCR2 in Inflammatory Conditions of the Central Nervous System

“…47 Monocytes from aging individuals have been reported to have impaired phagocytosis and increased levels of intracellular tumor necrosis factor-a, suggesting a dysregulation of monocyte function may exist in the aging population. 48 Together, the evidence currently suggests that Alzheimer's disease might involve impaired immune cell regulation involving CCR2.…”