A proteomic signature of healthspan

C Chia-Ling Kuo (Department of Public Health Sciences, University of Connecticut Health Center) P Peiran Liu (Biostatistics Center, The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut Health Center) G Gabin Drouard (Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki) E Eero Vuoksimaa (Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki) J Jaakko Kaprio M Miina Ollikainen (Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki) Z Zhiduo Chen (University of Connecticut Center on Aging, University of Connecticut Health Center) L Luke C. Pilling (Department of Clinical and Biomedical Sciences, University of Exeter) J Janice L. Atkins (Department of Clinical and Biomedical Sciences, University of Exeter) R Richard H. Fortinsky (University of Connecticut Center on Aging, University of Connecticut Health Center) G George A. Kuchel (University of Connecticut Center on Aging, University of Connecticut Health Center) B Breno S. Diniz (Department of Public Health Sciences, University of Connecticut Health Center)

Abstract

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 proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2,920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as chronic obstructive pulmonary disease, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to other biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. The external validity was evaluated using the Essential Hypertension Epigenetics study with proteomic data also from the Olink Explore 3072 and complementary epigenetic data, making it a valuable tool for assessing healthspan and as a potential surrogate marker to complement existing proteomic and epigenetic biological age measures in geroscience-guided studies.

Article Details

Volume / Issue Vol. 122, Issue 23
Published June 10, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (12)

C

Chia-Ling Kuo

Department of Public Health Sciences, University of Connecticut Health Center

P

Peiran Liu

Biostatistics Center, The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut Health Center

G

Gabin Drouard

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki

E

Eero Vuoksimaa

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki

J

Jaakko Kaprio

M

Miina Ollikainen

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki

Z

Zhiduo Chen

University of Connecticut Center on Aging, University of Connecticut Health Center

L

Luke C. Pilling

Department of Clinical and Biomedical Sciences, University of Exeter

J

Janice L. Atkins

Department of Clinical and Biomedical Sciences, University of Exeter

R

Richard H. Fortinsky

University of Connecticut Center on Aging, University of Connecticut Health Center

G

George A. Kuchel

University of Connecticut Center on Aging, University of Connecticut Health Center

B

Breno S. Diniz

Department of Public Health Sciences, University of Connecticut Health Center