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van Sleen, Y.

Publications and source records attributed to van Sleen, Y..

2 recordsLinked to original sources
bioRxiv2023

Frailty is related to serum inflammageing markers: results from the VITAL study

Frailty describes an age-associated state in individuals with an increased vulnerability and less resilience against adverse outcomes. To score frailty, studies have employed the questionnaires, such as the SF-36 and EQ-5D-3L, or the Frailty Index, a composite score based on deficit accumulation. Furthermore, ageing of the immune system is often accompanied by a state of low-grade inflammation (inflammageing). Here, we aimed to associate 29 circulating markers of inflammageing with frailty measures in a prospective cohort study to understand the mechanisms underlying ageing. Frailty measures and inflammageing markers were assessed in 317 participants aged 25-90. We determined four different measures of frailty: the Frailty Index based on 31 deficits, the EQ-5D-3L and two physical domains of the SF-36. Serum/plasma levels of inflammageing markers and CMV/EBV seropositivity were measured using different techniques: Quanterix, Luminex or ELISA. All four measures of frailty strongly correlated with age and BMI. Nineteen biomarkers correlated with age, some in a linear fashion (IL-6, YKL-40), some only in the oldest age brackets (CRP), and some increased at younger ages and then plateaued (CCL2, sIL-6R). After correcting for age, biomarkers, such as IL-6, CRP, IL-1RA, YKL-40 and elastase, were associated with frailty. When corrected for BMI, the number of associations reduced further. In conclusion, inflammageing markers, particularly markers reflecting innate immune activation, are related to frailty. These findings indicate that health decline and the accumulation of deficits with age is accompanied with a low-grade inflammation which can be detected by specific inflammatory markers.

immunology↗
bioRxiv2023

Effects of ageing and frailty on circulating monocyte and dendritic cell subsets

Ageing is associated with dysregulated immune responses, resulting in impaired resilience against infections and a low-grade inflammation known as inflammageing. Frailty is a measurable condition in older adults characterized by decreased health and physical impairment. Dendritic cells (DCs) and monocytes play a crucial role in initiating and steering immune responses. To assess whether their frequencies and phenotypes in the blood are affected by ageing or frailty, we performed a flow cytometry study (14 markers) on monocyte and DC subsets in an immune ageing cohort (SENEX). Participants were divided into three groups (n=15 each): healthy young controls (HYC, median age 29 years), healthy older controls (HOC, 73 years) and Frail older controls (76 years). Frailty status was based on Tilburg Frailty Index scores. Among HLA-DR+/CD19-cells, monocyte subsets (classical, intermediate, non-classical) were identified by CD14 and CD16 expression, and DC subsets (conventional (c)DC1, cDC2, plasmacytoid (p)DC) by CD11c, CD1c, CD141 and CD303 expression. Using unsupervised and conventional gating strategies, we observed a substantially lower proportion of pDCs in the HOC compared to the HYC. Additionally, we observed higher expression of activation markers on classical and intermediate monocytes and on cDC2 in HOC compared to HYC. Comparing the Frail to the age-matched HOC group, we observed only one important difference: a higher expression of CD40 on classical and non-classical monocytes in Frail individuals. In this cross-sectional study, we document a substantial effect of ageing on monocytes and DCs. The reduction of pDCs in older people may underly their impaired ability to counter viral infections, whereas the enhanced expression of activation markers could indicate a state of inflammageing. Future studies could elucidate the functional consequences of CD40 upregulation with frailty.

immunology↗