There are major differences in how individuals and their immune systems respond to ageing. The frailty phenotype is used to describe older adults with a declining health and signifies an increased vulnerability to adverse outcomes, most notably: physical impairment, disease and mortality.
Frailty largely concerns the ability of an organism to cope with outside stressors , and is found more often in those with comorbidities and in those in long-term care. Frailty is a dynamic state which tends to increase with age, but can also fluctuate over time. The golden standard for measuring an individual’s frailty, is the Frailty Index as described by Rockwood and Mitnitski, which is known to be a better predictor of hospitalization and mortality than age by itself. The Frailty Index has now been adapted specifically for the VITAL cohort and contains 31 deficits on a range of physical systems.
Ageing of the immune system leads to a number of profound changes to the composition of leukocyte subsets and their functioning. A higher age has been associated with an increased level of chronic inflammation, evidenced by elevated C-reactive protein (CRP) levels; this process is also known as inflammageing . Inflammageing is typically characterized by an enhanced innate immune response. Considering the accumulation of deficits in frail individuals, we hypothesize that inflammageing may occur at a different speed in frail and non-frail individuals. To this end we linked frailty phenotypes and 29 serum markers of inflammageing in participants of the VITAL study, a nice collaborative effort between the partners INSERM (Paris) and University Medical Center in Groningen (UMCG).
We observed that the frailty index correlated strongly with age. Therefore, we had to correct for age to identify markers that reflect differences in frailty among individuals of the same age. We found a number of interesting associations of inflammageing markers with the Frailty Index:
–IL-6 and CRP. The pro-inflammatory cytokine IL-6 and the closely related acute-phase marker CRP have often been proposed as potential markers of frailty. However, the association between IL-6/CRP levels and frailty may partly be explained by the close interplay with the BMI.
–YKL-40. YKL-40 is produced by certain types of neutrophils and macrophages and was previously found to play a role in orchestrating tissue damage and angiogenesis. As a biomarker that likely reflects microglial activation, YKL-40 has been associated with a neurodegenerative diseases, including a role as a prognostic marker.
–IL-1RA. This antagonist of pro-inflammatory IL-1 signaling is typically released after stimulation by inflammatory mediators including IL-1β and IL-6, in which is thought of as a negative feedback mechanism. Previously, IL-1RA levels have been associated with the risk for cardiovascular disease, which likely plays a prominent role in frailty.
-Elastase. This was the only inflammageing marker that negatively associated with frailty: frail people had lower elastase levels than non-frail people. One earlier study had already shown that neutrophils, the main elastase producers, show dysfunction in frail people.
These data will be assembled into a manuscript that will be send out for publication early next year.