ABSTRACT Frailty is an age‐related syndrome characterized by an increased vulnerability to adverse health outcomes in the face of stressors. By deriving a blood‐based proteomic signature for frailty, the current study aimed to enhance the understanding of frailty biology and created a person‐specific predictor for the risk of frailty and other adverse age‐related health outcomes. A 25‐protein signature (proteomic frailty index pFI) predictive of the cumulative frailty index (FI) in the LonGenity cohort was derived using a penalized regression method. The pFI was significantly correlated with the FI at baseline (Pearson r = 0.58) and showed significant associations with age‐related chronic conditions, incident mortality, and clinical measures. In an independent cohort of 5195 participants in the Atherosclerosis Risk in Communities study, pFI was successfully validated with measured FI ( r = 0.61, p < 0.001) and was associated with physical frailty at baseline ( p < 0.001). The pFI was significantly associated with physical, clinical, and cognitive measures, as well as incident mortality (HR 95% CI = 1.13 1.12–1.14) and dementia (HR 95% CI = 1.07 1.05–1.09) after accounting for demographic factors. The pFI was further validated against FI ( r = 0.45, p < 0.001) in a second independent study in 654 participants from the Baltimore Longitudinal Study of Aging. In conclusion, we identified and validated a 25‐protein signature as an index of frailty that also captures overall well‐being, health, and risk for key age‐related diseases.
Sathyan et al. (Mon,) studied this question.