Back

ProtFI, an efficient frailty-trained proteomics-based biomarker of aging, robustly2 predicts age-related decline

Garst, S.; Kuiper, L. M.; van den Akker, E. B.; Berg, N. v. d.; Ghanbari, M.; Mooijaart, S. P.; Beekman, M.; Reinders, M.; Slagboom, P. E.; van Meurs, J.

2025-09-30 health informatics
10.1101/2025.09.19.25336152 medRxiv
Show abstract

Chronological age overlooks the heterogeneity in aging. In response, a wide range of molecular aging biomarkers has been developed to better capture an individual"s aging rate. Yet, a comprehensive comparison of modeling choices in the development of these biomarkers is lacking. In this study, we trained aging biomarkers on the Rockwood frailty index (FI) and all-cause mortality using UK Biobank Olink proteomics and metabolomics (1H-NMR) data (n=40,696). We systematically established the impact of model choice, target outcome, and molecular data source on several age-related outcomes. From this, we developed ProteinFrailty (ProtFI), an elastic net model using a minimal set of proteins to predict FI. ProtFI outperformed established aging biomarkers in relation to diverse outcomes, including incident cardiovascular disease, handgrip strength, and self-rated health, both in internal validation and two Dutch external cohorts (n=995, n=500). Our findings show that an efficient frailty-trained proteomic biomarker robustly predicts age-related decline.

Published in Cell Reports Methods · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.