These authors contributed equally to this work.
Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function
Article first published online: 20 JUL 2012
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 11, Issue 5, pages 867–875, October 2012
How to Cite
Hearps, A. C., Martin, G. E., Angelovich, T. A., Cheng, W.-J., Maisa, A., Landay, A. L., Jaworowski, A. and Crowe, S. M. (2012), Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell, 11: 867–875. doi: 10.1111/j.1474-9726.2012.00851.x
- Issue published online: 16 SEP 2012
- Article first published online: 20 JUL 2012
- Accepted manuscript online: 18 JUN 2012 03:10PM EST
- Accepted for publication 13 June 2012
- innate immunity;
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.