Organ aging signatures in the plasma proteome track health and disease

Hamilton Se-Hwee Oh, Jarod Rutledge, Daniel Nachun, Róbert Pálovics, Olamide Abiose, Patricia Moran-Losada, Divya Channappa, Deniz Yagmur Urey, Kate Kim, Yun Ju Sung, Lihua Wang, Jigyasha Timsina, Dan Western, Menghan Liu, Pat Kohlfeld, John Budde, Edward N. Wilson, Yann Guen, Taylor M. Maurer, Michael Haney, Andrew C. Yang, Zihuai He, Michael D. Greicius, Katrin I. Andreasson, Sanish Sathyan, Erica F. Weiss, Sofiya Milman, Nir Barzilai, Carlos Cruchaga, Anthony D. Wagner, Elizabeth Mormino, Benoit Lehallier, Victor W. Henderson, Frank M. Longo, Stephen B. Montgomery and Tony Wyss-Coray ()
Additional contact information
Hamilton Se-Hwee Oh: Stanford University
Jarod Rutledge: Stanford University
Daniel Nachun: Stanford University School of Medicine
Róbert Pálovics: Stanford University
Olamide Abiose: Stanford University
Patricia Moran-Losada: Stanford University
Divya Channappa: Stanford University
Deniz Yagmur Urey: Stanford University
Kate Kim: Stanford University
Yun Ju Sung: Washington University in St Louis
Lihua Wang: Washington University in St Louis
Jigyasha Timsina: Washington University in St Louis
Dan Western: Washington University in St Louis
Menghan Liu: Washington University in St Louis
Pat Kohlfeld: Washington University in St Louis
John Budde: Washington University in St Louis
Edward N. Wilson: Stanford University
Yann Guen: Stanford University School of Medicine
Taylor M. Maurer: Stanford University School of Medicine
Michael Haney: Stanford University
Andrew C. Yang: University of California San Francisco
Zihuai He: Stanford University School of Medicine
Michael D. Greicius: Stanford University School of Medicine
Katrin I. Andreasson: Stanford University
Sanish Sathyan: Albert Einstein College of Medicine
Erica F. Weiss: Montefiore Medical Center
Sofiya Milman: Albert Einstein College of Medicine
Nir Barzilai: Albert Einstein College of Medicine
Carlos Cruchaga: Washington University in St Louis
Anthony D. Wagner: Stanford University
Elizabeth Mormino: Stanford University School of Medicine
Benoit Lehallier: Stanford University School of Medicine
Victor W. Henderson: Stanford University
Frank M. Longo: Stanford University
Stephen B. Montgomery: Stanford University School of Medicine
Tony Wyss-Coray: Stanford University

Nature, 2023, vol. 624, issue 7990, 164-172

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-023-06802-1

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