Relation of inflammatory marker trajectories with frailty and aging in a 20-year longitudinal study

Abstract

Little is known about the development of low-grade inflammation with age and its relationship with the onset of frailty. In this exploratory study, we investigated 18 inflammatory markers measured in blood of 148 individuals aged 65-75 years at study endpoint, collected over 20 years at five-year intervals. IFNγ- and platelet activation markers changed in synchrony over time. Chronically elevated levels of IL-6-related markers, such as CRP and sIL-6R, were associated with frailty and becoming frail over time, ,poorer lung function or less physical strength. Overweight was a possible driver of these associations. More and stronger associations were detected in women, such as between increasing sCD14 levels and frailty, indicating possible monocyte overactivation. Multivariate prediction of frailty showed low accuracy but confirmed the main results. In summary, we documented 20-year temporal changes in and between inflammatory markers in an aging population, and related these to clinically relevant health outcomes.

Association among Terminally Differentiated T Cells, Frailty, and Dependency in a Group of Cuban Centenarians

“…Serum IL-6 and were undetectable in most centenarians. This finding contrasts with most of the literature that supports an increase in inflammatory markers with age [8,15,17,18,30,[33][34][35]. Additionally, serum cytokine (IL-6 and TNF-α) and CRP levels did not show association with frailty, or any other clinical feature, probably due to the fact that most centenarians had cytokine levels under the detection limit.…”

“…Cao and colleagues described that pre-frail subjects showed higher proportion of differentiated memory phenotypes and lower proportion of naive subsets in the CD8+ compartment, when compared to robust elder persons [14]. Frailty indexes have been vastly used as a tool to predict morbidity and mortality in the elderly [16, 34, 35]. The lower concentrations of total protein and iron levels found in frail centenarians were an expected result since hypoproteinemia and anemia are closely related to sarcopenia and frailty [33, 40].…”

The impact of ageing on monocytes and macrophages

“…Interestingly within the older adult population there are differences in monocyte number and function depending on the level of frailty. It has been observed that there is an increased overall number of monocytes in frail older adults as compared to those les frail older adults (139). Classical monocytes isolated from frail older adults had increased inflammatory associated genes in response to LPS as compared to non-frail older adults (140).…”

Impaired JAK-STAT Pathway Signaling in Leukocytes of Frail Elderly

“…During each measurement round, plasma samples were taken and information regarding the participants' health was collected. The present analysis is based on a sample of 16 men and 18 women who were 65-75 years of age, selected from a subgroup of DCS participants in which we previously analyzed in ammatory marker trajectories (43). The latter were still active in the DCS at least until 2016, had at least 5 plasma samples available from previous rounds, were CMV seronegative at last measurement, and did not use immunosuppressants.…”

“…To quantify low-grade in ammation, we measured a panel of ammatory markers in 5 repeated blood samples per individual that were withdrawn at 5-year intervals over the period of approximately 20 years; details are described elsewhere (43). The panel consists of the following cytokines, chemokines and soluble receptors: C-C Motif Chemokine Ligand (CCL) 1/I-309, CCL2/MCP-1, CCL5/RANTES, CCL11/Eotaxin, CCL27/C-TACK, C-X-C Motif Chemokine Ligand (CXCL) 9 /MIG, CXCL10/IP-10, CXCL11/I-TAC, IL-10, IL-6, soluble CD40 ligand (sCD40L), soluble CD14 (sCD14), soluble IL-6 receptor (sIL-6R), glycoprotein 130 (GP130), Complement 5a (C5a), Brain-derived neurotrophic factor (BDNF), and soluble P-selectin.…”