오세휘 (Stanford University) | 한빛사논문 > 한빛사

한빛사논문

조회1,114

오세휘Hamilton Se-Hwee Oh

Stanford University

CV File 153 kb

Nature, Dec 2023, 624 (7990) | https://doi.org/10.1038/s41586-023-06802-1 Organ aging signatures in the plasma proteome track health and disease

Hamilton Se-Hwee Oh^1,2,3,22, Jarod Rutledge^2,3,4,22, Daniel Nachun⁵, Róbert Pálovics^2,3,6, Olamide Abiose^3,6, Patricia Moran-Losada^2,3,6, Divya Channappa^2,3,6, Deniz Yagmur Urey^2,7, Kate Kim^2,3,6, Yun Ju Sung^8,9, Lihua Wang^8,9, Jigyasha Timsina^8,9, Dan Western^8,9,10, Menghan Liu^8,9, Pat Kohlfeld^8,9, John Budde^8,9, Edward N. Wilson^3,6, Yann Guen^6,11, Taylor M. Maurer⁵, Michael Haney^2,3,6, Andrew C. Yang^12,13,14, Zihuai He⁶, Michael D. Greicius⁶, Katrin I. Andreasson^3,6,15, Sanish Sathyan¹⁶, Erica F. Weiss¹⁷, Sofiya Milman¹⁶, Nir Barzilai¹⁶, Carlos Cruchaga^8,9, Anthony D. Wagner^3,18, Elizabeth Mormino⁶, Benoit Lehallier⁶, Victor W. Henderson^3,6,19, Frank M. Longo^3,6, Stephen B. Montgomery^5,20,21& Tony Wyss-Coray^2,3,6

¹Graduate Program in Stem Cell and Regenerative Medicine, Stanford University, Stanford, CA, USA.

²The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.

³Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.

⁴Graduate Program in Genetics, Stanford University, Stanford, CA, USA.

⁵Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

⁶Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.

⁷Department of Bioengineering, Stanford University School of Engineering, Stanford, CA, USA.

⁸Department of Psychiatry, Washington University in St Louis, St Louis, MO, USA.

⁹NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.

¹⁰Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.

¹¹Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

¹²Departments of Neurology and Anatomy, University of California San Francisco, San Francisco, CA, USA.

¹³Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.

¹⁴Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA, USA.

¹⁵Chan Zuckerberg Biohub, San Francisco, CA, USA.

¹⁶Departments of Medicine and Genetics, Institute for Aging Research, Albert Einstein College of Medicine, New York, NY, USA.

¹⁷Department of Neurology, Montefiore Medical Center, New York, NY, USA.

¹⁸Department of Psychology, Stanford University, Stanford, CA, USA.

¹⁹Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.

²⁰Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

²¹Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.

²²These authors contributed equally: Hamilton Se-Hwee Oh, Jarod Rutledge.

Corresponding author : Correspondence to Tony Wyss-Coray.

Abstract

Animal studies show aging varies between individuals as well as between organs within an individual ^1-4, 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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-11)
연구진국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기