Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

doi:10.1016/j.cell.2025.06.047

. 2025 Jul 22:S0092-8674(25)00749-4.

doi: 10.1016/j.cell.2025.06.047. Online ahead of print.

Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

Yingjie Ding¹, Yuesheng Zuo¹, Bin Zhang², Yanling Fan³, Gang Xu⁴, Zhongyi Cheng⁵, Shuai Ma⁶, Shuaiqi Fang², Ao Tian², Dandan Gao⁷, Xi Xu⁴, Qiaoran Wang¹, Yaobin Jing⁸, Mengmeng Jiang⁹, Muzhao Xiong¹, Jiaming Li¹, Zichu Han¹, Shuhui Sun¹⁰, Si Wang¹¹, Fuchu He¹², Jiayin Yang¹³, Jing Qu¹⁴, Weiqi Zhang¹⁵, Guang-Hui Liu¹⁶

Affiliations

¹ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁴ Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu 610000, China; Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu 610000, China.
⁵ Jingjie PTM BioLab (Hangzhou) Co., Inc., HangZhou 310000, China.
⁶ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China.
⁷ Department of Respiratory and Critical Care, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
⁸ International Center for Aging and Cancer, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China.
⁹ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
¹⁰ Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China.
¹¹ Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Aging Biomarker Consortium (ABC), Beijing 100101, China.
¹² State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102200, China.
¹³ Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu 610000, China; Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu 610000, China. Electronic address: doctoryjy@scu.edu.cn.
¹⁴ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: qujing@ioz.ac.cn.
¹⁵ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: zhangwq@big.ac.cn.
¹⁶ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: ghliu@ioz.ac.cn.

PMID: 40713952
DOI: 10.1016/j.cell.2025.06.047

Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

Yingjie Ding et al. Cell. 2025.

. 2025 Jul 22:S0092-8674(25)00749-4.

doi: 10.1016/j.cell.2025.06.047. Online ahead of print.

Authors

Affiliations

¹ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁴ Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu 610000, China; Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu 610000, China.
⁵ Jingjie PTM BioLab (Hangzhou) Co., Inc., HangZhou 310000, China.
⁶ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China.
⁷ Department of Respiratory and Critical Care, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
⁸ International Center for Aging and Cancer, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China.
⁹ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
¹⁰ Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China.
¹¹ Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Aging Biomarker Consortium (ABC), Beijing 100101, China.
¹² State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102200, China.
¹³ Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu 610000, China; Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu 610000, China. Electronic address: doctoryjy@scu.edu.cn.
¹⁴ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: qujing@ioz.ac.cn.
¹⁵ China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: zhangwq@big.ac.cn.
¹⁶ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Aging Biomarker Consortium (ABC), Beijing 100101, China. Electronic address: ghliu@ioz.ac.cn.

PMID: 40713952
DOI: 10.1016/j.cell.2025.06.047

Abstract

Proteins are the cornerstone of life. However, the proteomic blueprint of aging across human tissues remains uncharted. Here, we present a comprehensive proteomic and histological analysis of 516 samples from 13 human tissues spanning five decades. This dynamic atlas reveals widespread transcriptome-proteome decoupling and proteostasis decline, characterized by amyloid accumulation. Based on aging-associated protein changes, we developed tissue-specific proteomic age clocks and characterized organ-level aging trajectories. Temporal analysis revealed an aging inflection around age 50, with blood vessels being a tissue that ages early and is markedly susceptible to aging. We further defined a plasma proteomic signature of aging that matches its tissue origins and identified candidate senoproteins, including GAS6, driving vascular and systemic aging. Together, our findings lay the groundwork for a systems-level understanding of human aging through the lens of proteins.

Keywords: aging; aging clock; amyloid; biomarker; inflammation; protein; proteomics; senokine; senoprotein; vascular aging.

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Conflict of interest statement

Declaration of interests Z.C. is an employee of Jingjie PTM BioLab (Hangzhou) Co. Inc.

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Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

Affiliations

Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

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