Organ aging signatures in the plasma proteome track health and disease
- PMID: 38057571
- PMCID: PMC10700136
- DOI: 10.1038/s41586-023-06802-1
Organ aging signatures in the plasma proteome track health and disease
Abstract
Animal studies show aging varies between individuals as well as between organs within an individual1-4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20-50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer's disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.
© 2023. The Author(s).
Conflict of interest statement
T.W-C., H.O., J.R., B.L. and Stanford University have filed a patent application related to this work, PCT/US2023/027896. T.W-C., H.O. and J.R. are co-founders and scientific advisors of Teal Omics Inc. and have received equity stakes. T.W.-C. is a co-founder and scientific advisor of Alkahest Inc. and Qinotto Inc. and has received equity stakes in these companies. C.C. has received research support from GSK and EISAI. The funders of the study had no role in the collection, analysis or interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. C.C. is a member of the advisory board of Vivid Genomics and Circular Genomics and owns stocks in these companies. S.B.M is a consultant for BioMarin, MyOme and Tenaya Therapeutics. All other authors have certified they have no competing interests to declare.
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