Proteomic aging clocks in epidemiological studies: advances, applications and prospects

Biological age may provide a more informative metric of individual physiological function and life expectancy, compared to chronological age. Proteomic aging clocks are predictive models trained using high-dimensional proteomic data to quantify biological age. Owing to the central biological role of proteins and their established clinical utility as druggable targets and prognostic biomarkers, proteomics is particularly promising for the assessment of aging. In this Review, we provide an overview of current proteomic clocks based on different platforms in human blood samples, emphasizing their potential clinical application as discovery, predictive and response aging biomarkers. While the field is advancing rapidly, proteomic clocks vary widely in their assay platforms, study populations and modeling strategies, which may limit their generalizability, biological interpretability and translational utility. We further discuss current challenges and prospects in this research area, which aims to facilitate the implementation of proteomic clocks in proactive, preventive medicine to extend population healthspan.