Our results indicate that for many, but not all myeloid cell populations, age-related alterations tend to become more pronounced with advanced-age and frailty. These changes in WIKI4 circulating myeloid cell populations may reflect changes in precursor generation or emigration from the bone marrow. As an example, the recent finding in mice that a Genkwanin reduction of circulating pDCs stimulates myelopoiesis and increases circulating myeloid-derived suppressor cells, whose numbers increase in the advanced-age, frail elderly, implies that there may be previously unappreciated feedback mechanisms between circulating DCs and the bone marrow compartment. In addition to changes in frequency, changes in phenotype and function have been shown to occur with age and it has been proposed that these phenotypic changes may contribute to ageassociated chronic disease, especially those with inflammatory etiology. There have been conflicting reports, for example, as to whether monocytes have hypo- or hyper-inflammatory responses to TLR ligands and whether these might be due to changes in TLR expression. While we observed only a slight increase in the percentage of TLR-4 expressing classical monocytes and no changes to the expression of monocyte TLR-2, the production of TNF, and to a lesser extent IL-8, was significantly higher in monocyte subsets from the advanced-age, frail elderly, both at baseline and in response to TLR-2 and -4 stimuli. This is similar to what has been shown in previous reports, and supports the theory that constitutive over-production of cytokines by monocyte subsets may predispose elderly individuals to a higher risk of chronic disease. Another potential contributor to the development of chronic disease in the elderly is the ability of circulating monocytes to migrate to the tissues. Both CCR2 and CX3CR1, receptors for the chemokines MCP-1 and fractalkine, are potently involved in the migration and recruitment of monocytes in the host.Chronic inflammation anemia is extremely common in the frail elderly and is associated with elevated levels of inflammatory cytokines, especially IL-6.