Inflammatory marker trajectories associated with frailty and ageing in a 20‐year longitudinal study

Abstract

Objective The aim of this exploratory study was to investigate the development of low‐grade inflammation during ageing and its relationship with frailty. Methods The trajectories of 18 inflammatory markers measured in blood samples, collected at 5‐year intervals over a period of 20 years from 144 individuals aged 65–75 years at the study endpoint, were related to the degree of frailty later in life. Results IFN‐γ‐related markers and platelet activation markers were found to change in synchrony. Chronically elevated levels of IL‐6 pathway markers, such as CRP and sIL‐6R, were associated with more frailty, poorer lung function and reduced physical strength. Being overweight was a possible driver of these associations. More and stronger associations were detected in women, such as a relation between increasing sCD14 levels and frailty, indicating a possible role for monocyte overactivation. Multivariate prediction of frailty confirmed the main results, but predictive accuracy was low. Conclusion In summary, we documented temporal changes in and between inflammatory markers in an ageing population over a period of 20 years, and related these to clinically relevant health outcomes.

Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study

“…Also, the two commonly used definitions of frailty are very different and should rather be used as complementary frailty tools than substitutions for each other [ 49 ]. Our findings of an association between inflammation and frailty measured as FI as well as an association between frailty and monocyte-specific gene expression is supported by previous findings of an association between CRP and IL-6 with frailty using both Fried’s [ 25 , 26 , 38 , 39 ] and FI definition [ 9 ].…”

“…Higher levels of cathepsin S have shown to be associated with pro-inflammatory markers [ 36 ], as well as higher levels of CRP and IL-6 [ 37 ]. Furthermore, longitudinal studies have shown that chronic inflammation is associated with frailty, especially in women [ 9 , 38 ]. In midlife, stable low levels of CRP were linked to lower odds of frailty in later life [ 39 ].…”

“…To the best of our knowledge, only a few studies have examined the association between frailty, using the FI definition, and inflammatory markers. One study on subjects aged 65–75 years at the study endpoint showed significant associations between low-grade inflammation and FI [ 9 ]. Another study showed an association between CRP trajectories over a follow-up time of more than 15 years and FI, in subjects aged 60–85 at endpoint [ 10 ].…”

Multisystem physiological perspective of human frailty and its modulation by physical activity

“…The data revealed that elevated levels of IL-6 pathway markers, namely CRP and sIL-6R, were associated with more frailty and reduced physical strength. Other associations were detected in women, notably increasing sCD14 levels and frailty, an indicator of monocyte overactivation ( 287 ). In contrast, in a recent longitudinal study of a large birth cohort ( n = 1,091) the physical frailty phenotype and frailty index were both used to assess frailty in participants 12 yr apart.…”

Vitamin K Contribution to DNA Damage—Advantage or Disadvantage? A Human Health Response

“…Moreover, K1 treatment was shown to reduce the expression of interleukin-6 (IL-6) mRNA in THP-1 cells (human macrophages) treated with LPS [ 33 ]. IL-6 has been implicated in the pathology of a wide range of diseases, including coronary artery disease (CAD) [ 37 ], which contributes to diabetes [ 38 ], aging [ 39 , 40 ] and cancer progression [ 41 ]. IL-6 activates major signaling pathways: the Janus-activated kinase-signal transducer and activator of transcription (JAK)-STAT) pathways, the Ras/Raf mitogen-activated protein kinase (MAPK, MEK/ERK) signaling cascade, and the phosphatidylinositol 3-kinase-dependent (PI3K/AKT) pathway [ 42 , 43 , 44 ].…”