Yannick van Sleen^1*, Sudarshan A. Shetty¹, Marieke van der Heiden¹, Milou C. A. Venema¹, Nicolas Gutiérrez‑Melo², Erik J. M. Toonen³, Josine van Beek⁴, Anne‑Marie Buisman⁴, Debbie van Baarle¹ and Delphine Sauce²

Abstract
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 lowgrade inflammation which can be detected by specific inflammatory markers.

Keywords Ageing, Frailty, Inflammation, Biomarkers, Body Mass Index, Cytomegalovirus

NON-2024-1446