期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 71, 期 5, 页码 610-618出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glv121
关键词
Inflammation; Aging; Monocyte function; CMV; Cognitive; Mini-mental
资金
- Redes Tematicas de Investigacion en SIDA [ISCIII RETIC RD12/0017/0029, RD06/0006/0035]
- Proyecto de Excelencia, Consejeria de Innovacion, Ciencia y Empresa [P11-CTS-06313]
- Consejeria Andaluza de Salud [PI-0278-2010]
- Instituto de Salud Carlos III [CPII014/00025]
- Ministry of Economy and Competitiveness [RYC-2010-07419]
Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (alpha), IL1-beta (beta), IL-6, IL-8, TNF-alpha, and IL-10 of elderly adults (median 83 [67-90] years old; n = 20) compared with young controls (median 35 [27-40] years old; n = 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-alpha (p = .001), IL1-beta (p = .001), IL-6 (p = .002), and IL-8 (p = .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline.
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