| Title: | ProtFI, an efficient frailty-trained proteomics-based biomarker of aging, robustly predicts age-related decline |
| Journal: | Cell Reports Methods |
| Published: | 10 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41966686/ |
| DOI: | https://doi.org/10.1016/j.crmeth.2026.101405 |
Publication 18038
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Many molecular aging biomarkers have been developed to capture heterogeneity in individual aging rates. Yet, systematic comparison of the modeling choices underlying these biomarkers has been limited. 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 two aging biomarkers, ProteinFrailty (ProtFI) and ProteinMortality (ProtMort), which are both ElasticNet models that use a minimal set of proteins to predict FI and mortality, respectively. In particular, 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.</p>
10 Authors
- Swier Garst
- Lieke Kuiper
- Erik van den Akker
- Niels van den Berg
- Mohsen Ghanbari
- Simon Mooijaart
- Marian Beekman
- Marcel Reinders
- P Eline Slagboom
- Joyce van Meurs
1 Application
| Application ID | Title |
|---|---|
| 67864 | Polygenic risk score transportability across populations and complex traits: characterizing clinical applications of risk profiles within the context of the Genotyping Of ALL (GOALL) project |
Enabling scientific discoveries that improve human health