The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using data from the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to chronological age and biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. Our findings demonstrate the validity of HPS, making it a valuable tool for assessing healthspan and as a potential surrogate marker in geroscience-guided studies.

The authors have declared no competing interest.

Access to UK Biobank data was granted under application no. 92647 "Research to Inform the Field of Precision Gerontology" (PI: Richard H. Fortinsky), funded by the Claude D. Pepper Older American Independence Centers (OAIC) program: P30AG067988 (MPIs: George A. Kuchel and Richard H. Fortinsky). CLK, BSD, RHF, and GAK are partially supported by P30AG067988. JLA has a UK National Institute for Health and Care Research (NIHR) Advanced Fellowship (NIHR301844).

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Access to UK Biobank data was granted under application no. 92647 "Research to Inform the Field of Precision Gerontology" (PI: Richard H. Fortinsky).

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