Biomarker Signatures of Two Phenotypical Prefrailty Types in the Irish Longitudinal Study on Ageing

We investigated the biomarker signatures of two previously reported phenotypical prefrailty (PF) types in the first wave of The Irish Longitudinal Study on Ageing (TILDA): PF1 (unexplained weight loss and/or exhaustion) and PF2 (one or two among slowness, weakness, and low physical activity). Binary logistic regression models evaluated the independent associations between available plasma biomarkers and each PF type (compared to robust and compared to each other), while adjusting for age, sex, and education. A total of 5307 participants were included (median age 61 years, 53% women) of which 1473 (28%) were prefrail (469 PF1; 1004 PF2), 171 were frail, and 3663 were robust. The PF2 median age was eight years older than the PF1 median age. Higher levels of lutein and zeaxanthin were independently associated with the lower likelihood of PF1 (OR: 0.77, p < 0.001 and OR: 0.81, p < 0.001, respectively). Higher cystatin C was associated with PF1 (OR: 1.23, p = 0.001). CRP (OR: 1.19, p < 0.001), cystatin C (OR: 1.36, p < 0.001), and HbA1c (OR: 1.18, p < 0.001) were independently associated with PF2, while a higher total (OR: 0.89, p = 0.004) and HDL (OR: 0.87, p < 0.001) cholesterol seemed to be PF2-protective. While PF1 seemed to be inversely associated with serum carotenoid concentrations and hence has an oxidative signature, PF2 seemed to have pro-inflammatory, hyperglycemic, and hypolipidemic signatures. Both PF types were associated with higher cystatin C (lower kidney function), but no biomarkers significantly distinguished PF1 vs. PF2. Further research should elucidate whether therapies for different PF types may require targeting of different biological pathways.