Abstract
BackgroundCirculating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.DesignIn the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81–100 yrs), and compared against that of adults (19–59 yrs), and community-dwelling seniors (61–76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.ResultsThe advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.ConclusionsThese data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.
Highlights
Age-related changes in circulating immune cell composition and levels of circulating pro-inflammatory cytokines have been associated with longevity [1], frailty [2] and age-related diseases such as Alzheimer’s and Parkinson’s disease [3], and rheumatoid arthritis [4]
These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases
For our characterization of peripheral blood monocyte and dendritic cells (DCs) subsets in the advanced-age, frail elderly, we included a cohort of young adults and community-dwelling seniors in order to ascertain whether the cellular frequency and receptor expression levels observed are consistent with alterations that occur over the course of aging, or if they are particular to advanced-age, frail elderly individuals
Summary
Age-related changes in circulating immune cell composition and levels of circulating pro-inflammatory cytokines have been associated with longevity [1], frailty [2] and age-related diseases such as Alzheimer’s and Parkinson’s disease [3], and rheumatoid arthritis [4]. For individuals that are susceptible to developing infectious or chronic disease, such as the advanced-age, frail elderly, alterations to these cellular populations may be a sensitive biomarker in determining their level of risk These markers could include the frequency of a given cellular subset in the circulation, the expression of receptors that are critical for the migration to tissues via chemokine gradients or the innate response to pathogens, or potentially the ex vivo response to an exogenous stimuli. Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population
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