2. Academic Validation
  3. Comprehensive human proteome profiles across a 50-year lifespan reveal aging trajectories and signatures

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

  • Cell. 2025 Oct 2;188(20):5763-5784.e26. doi: 10.1016/j.cell.2025.06.047.
Yingjie Ding 1,  Yuesheng Zuo 1,  Bin Zhang 2,  Yanling Fan 3,  Gang Xu 4,  Zhongyi Cheng 5,  Shuai Ma 6,  Shuaiqi Fang 2,  Ao Tian 2,  Dandan Gao 7,  Xi Xu 4,  Qiaoran Wang 1,  Yaobin Jing 8,  Mengmeng Jiang 9,  Muzhao Xiong 1,  Jiaming Li 1,  Zichu Han 1,  Shuhui Sun 10,  Si Wang 11,  Fuchu He 12,  Jiayin Yang 13,  Jing Qu 14,  Weiqi Zhang 15,  Guang-Hui Liu 16
Affiliations

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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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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