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 GenomicsChinese Academy of SciencesBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China.
² State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China.
³ China National Center for Bioinformation and Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China.
⁴ Liver Transplant CenterOrgan Transplant CenterWest China Hospital of Sichuan UniversityChengdu 610000China; Laboratory of Liver TransplantationKey Laboratory of Transplant Engineering and ImmunologyNHCWest China Hospital of Sichuan UniversityChengdu 610000China.
⁵ Jingjie PTM BioLab (Hangzhou) Co.Inc.HangZhou 310000China.
⁶ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China.
⁷ Department of Respiratory and Critical CareQuzhou Affiliated Hospital of Wenzhou Medical UniversityQuzhou People's HospitalQuzhou 324000China.
⁸ International Center for Aging and CancerHainan Academy of Medical SciencesHainan Medical UniversityHaikou 571199China.
⁹ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China.
¹⁰ Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLungand Blood Vessel DiseasesBeijing 100029China.
¹¹ Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersAging Translational Medicine CenterBeijing Municipal Geriatric Medical Research CenterBeijing Key Laboratory of Environment and AgingXuanwu Hospital Capital Medical UniversityBeijing 100053China; Aging Biomarker Consortium (ABC)Beijing 100101China.
¹² State Key Laboratory of Medical ProteomicsBeijing Proteome Research CenterNational Center for Protein Sciences (Beijing)Beijing Institute of LifeomicsBeijing 102200China.
¹³ Liver Transplant CenterOrgan Transplant CenterWest China Hospital of Sichuan UniversityChengdu 610000China; Laboratory of Liver TransplantationKey Laboratory of Transplant Engineering and ImmunologyNHCWest China Hospital of Sichuan UniversityChengdu 610000China. Electronic address: [email protected].
¹⁴ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLungand Blood Vessel DiseasesBeijing 100029China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].
¹⁵ China National Center for Bioinformation and Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].
¹⁶ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersAging Translational Medicine CenterBeijing Municipal Geriatric Medical Research CenterBeijing Key Laboratory of Environment and AgingXuanwu Hospital Capital Medical UniversityBeijing 100053China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].

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 Oct 2;188(20):5763-5784.e26.

doi: 10.1016/j.cell.2025.06.047. Epub 2025 Jul 25.

Authors

Affiliations

¹ China National Center for Bioinformation and Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China.
² State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China.
³ China National Center for Bioinformation and Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China.
⁴ Liver Transplant CenterOrgan Transplant CenterWest China Hospital of Sichuan UniversityChengdu 610000China; Laboratory of Liver TransplantationKey Laboratory of Transplant Engineering and ImmunologyNHCWest China Hospital of Sichuan UniversityChengdu 610000China.
⁵ Jingjie PTM BioLab (Hangzhou) Co.Inc.HangZhou 310000China.
⁶ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China.
⁷ Department of Respiratory and Critical CareQuzhou Affiliated Hospital of Wenzhou Medical UniversityQuzhou People's HospitalQuzhou 324000China.
⁸ International Center for Aging and CancerHainan Academy of Medical SciencesHainan Medical UniversityHaikou 571199China.
⁹ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China.
¹⁰ Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLungand Blood Vessel DiseasesBeijing 100029China.
¹¹ Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersAging Translational Medicine CenterBeijing Municipal Geriatric Medical Research CenterBeijing Key Laboratory of Environment and AgingXuanwu Hospital Capital Medical UniversityBeijing 100053China; Aging Biomarker Consortium (ABC)Beijing 100101China.
¹² State Key Laboratory of Medical ProteomicsBeijing Proteome Research CenterNational Center for Protein Sciences (Beijing)Beijing Institute of LifeomicsBeijing 102200China.
¹³ Liver Transplant CenterOrgan Transplant CenterWest China Hospital of Sichuan UniversityChengdu 610000China; Laboratory of Liver TransplantationKey Laboratory of Transplant Engineering and ImmunologyNHCWest China Hospital of Sichuan UniversityChengdu 610000China. Electronic address: [email protected].
¹⁴ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLungand Blood Vessel DiseasesBeijing 100029China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].
¹⁵ China National Center for Bioinformation and Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].
¹⁶ State Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China; University of Chinese Academy of SciencesBeijing 100049China; Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersAging Translational Medicine CenterBeijing Municipal Geriatric Medical Research CenterBeijing Key Laboratory of Environment and AgingXuanwu Hospital Capital Medical UniversityBeijing 100053China; Human Organ Physiopathology Emulation SystemInstitute of ZoologyChinese Academy of SciencesBeijing 100101China; Aging Biomarker Consortium (ABC)Beijing 100101China. Electronic address: [email protected].

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

Abstract

Proteins are the cornerstone of life. Howeverthe proteomic blueprint of aging across human tissues remains uncharted. Herewe 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 declinecharacterized by amyloid accumulation. Based on aging-associated protein changeswe developed tissue-specific proteomic age clocks and characterized organ-level aging trajectories. Temporal analysis revealed an aging inflection around age 50with 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 senoproteinsincluding GAS6driving vascular and systemic aging. Togetherour 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

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical