Multimodal clocks of human aging PMID: 42105758

ADC Targets in Oncology

2026-04-10

Multimodal clocks of human aging

Cell. 2026 Jul 9;189(14):4489-4511.e31. doi: 10.1016/j.cell.2026.04.025.

Jiaming Li ¹ , Beier Jiang ² , Wei Zhang ³ , Junwei Hao ⁴ , Zhili Liu ⁵ , Qianzhao Ji ⁶ , Yandong Zheng ⁷ , Xiaoyong Lu ¹ , Zikai Zheng ¹ , Shuai Ma ⁸ , Yanlin Fan ⁹ , Dan-Dan Gao ² , Xiao-Wen Hou ¹⁰ , Jing Li ¹¹ , Jiazhen Tang ⁵ , Yaobin Jing ¹² , Lingling Geng ⁷ , Ruochen Wu ¹³ , Baohu Zhang ¹³ , Shuhui Sun ¹⁴ , Yusheng Cai ¹⁵ , Kaowen Yan ¹⁵ , Muzhao Xiong ⁹ , Chen Dong ¹⁶ , Xibo Ma ¹⁷ , Gang Xu ¹⁸ , Zhejun Ji ⁶ , Haoteng Yan ⁷ , Quan Zheng ² , Honghao Huang ³ , Li Zhang ¹¹ , Junming Li ⁵ , Mengmeng Jiang ⁶ , Liu-Jun Xu ² , Yifan Chen ³ , Geyue Qu ¹¹ , Wan Lei ⁵ , Hengchao Wang ⁹ , Jun Ping ² , Jia Zhou ¹⁹ , Ming Yi ¹¹ , Mingjin Jiang ⁵ , Ying Jing ⁷ , Wei-Dong Ye ² , Xiao Zhang ¹⁰ , Xi Chu ²⁰ , Yuting He ⁵ , Qian Zhao ⁷ , Qi Wu ² , Meiling He ¹⁹ , Lina Ma ¹¹ , Peng Liu ⁵ , Liyun Zhao ⁷ , Qiao-Cheng Zhai ²¹ , Jun Qin ¹⁹ , Jie Lu ²² , Xianhe Yang ⁵ , Shuo Zhang ¹ , Yu Xiong ² , Hua Ren ¹⁹ , Wei Yang ¹¹ , Zhanmei Huang ⁵ , Jiachen Zhang ²³ , Min Zhang ²⁴ , Pei Chen ¹⁹ , Jian Dong ²⁰ , Yu Zhang ⁵ , Tingting Yan ²³ , Jin-Lin Ye ²¹ , Ping Huang ¹⁹ , Zhigang Qi ²² , Yong Liu ⁵ , Jichen Shuai ²³ , Cheng-Shui Chen ² , Ping Li ³ , Dawei Li ⁴ , Xiuhua Xu ⁵ , Xuexian Song ¹⁷ , Jingyi Li ⁸ , Jiale Ping ¹ , Jinghao Hu ²³ , Xiaoyan Sun ¹ , Jiaqi Ai ²³ , Zhengqin Wang ¹³ , Yuxin Zhang ¹³ , Peng Yang ¹ , Taixin Ning ²³ , Yan Yu ¹³ , Zan He ²³ , Hui Zhang ¹⁴ , Tianyang Zhang ¹ , Yuanhan Yang ¹³ , Qiaoran Wang ⁹ , Fangmin Lin ¹³ , Xiangmei Jin ¹⁵ , Xuewei Chen ¹⁵ , Jie Ren ²⁵ , Moshi Song ²⁶ , Si Wang ²⁷ , Jiayin Yang ²⁸ , Jianming Li ⁵ , Weihong Song ²⁹ , Fuchu He ³⁰ , Yun-Gui Yang ³¹ , Gang Pei ³² , Jing Qu ³³ , Wei Zhang ³⁴ , Jun Pu ³⁵ , Feng Zhang ³⁶ , Guoguang Zhao ³⁷ , Weiqi Zhang ³⁸ , Guang-Hui Liu ³⁹

Affiliations

1. Beijing Key Laboratory of Intelligent Governance and Application of Biological Big Data, 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. Department of Respiratory and Critical Care, Quzhou Key Laboratory of Aging Biology and Longevity Medicine, Zhejiang-Germany Joint Laboratory on Lung Injury Repair and Regeneration, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
3. Department of Cardiology, Renji Hospital, School of Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200127, China.
4. Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
5. The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
6. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
7. 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.
8. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
9. Beijing Key Laboratory of Intelligent Governance and Application of Biological Big Data, China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
10. Department of Cardiology, Renji Hospital, School of Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200127, China; Central Laboratory, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China.
11. Department of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
12. Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education, International Center for Aging and Cancer, Hainan Medical University, Haikou 571199, China.
13. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
14. Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
15. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
16. State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing 100876, China.
17. MAIS, State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China.
18. Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, China; Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu, China.
19. Central Laboratory, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China.
20. Health Management Center, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
21. Division of Orthopaedics, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
22. Department of Radiology and Nuclear Medicine, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
23. 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; Xuanwu Hospital Capital Medical University, Beijing 100053, China.
24. Department of Respiratory and Critical Care, Quzhou Key Laboratory of Aging Biology and Longevity Medicine, Zhejiang-Germany Joint Laboratory on Lung Injury Repair and Regeneration, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110122, China.
25. State Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
26. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
27. 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), Aging Biobank (ABB), Beijing, China.
28. Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, China; Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
29. Center for Geriatric Medicine, The First Affiliated Hospital and Oujiang Laboratory, Institute of Aging, Wenzhou Medical University, Wenzhou, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
30. State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing, China; International Academy of Phronesis Medicine (Guangdong), Guangzhou 510000, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
31. Beijing Key Laboratory of Intelligent Governance and Application of Biological Big Data, 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; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China.
32. The Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
33. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
34. The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
35. Department of Cardiology, Renji Hospital, School of Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200127, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
36. Department of Respiratory and Critical Care, Quzhou Key Laboratory of Aging Biology and Longevity Medicine, Zhejiang-Germany Joint Laboratory on Lung Injury Repair and Regeneration, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
37. Department of Neurosurgery, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
38. Beijing Key Laboratory of Intelligent Governance and Application of Biological Big Data, 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; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].
39. State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Aging Biomarker Consortium (ABC), Aging Biobank (ABB), Beijing, China. Electronic address: [email protected].

Abstract

Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18-91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the multimodal clock (MM-clock) with extensive parameter coverage and enhanced predictive precision, and organ-associated aging clocks. Cross-layer analysis demonstrates that plasma protein clocks not only capture chronological age but also serve as efficient proxies for systemic physiological capacity. Leveraging this framework for discovery, we identified the age-dependent accumulation of coagulation factors as a driver of multi-organ senescence and systemic inflammatory activation. This study provides a foundational framework that bridges molecular signatures with functional decline, identifies new biomarkers for aging assessment, and reveals a novel translational driver of aging.

Keywords

aging; aging clock; aging cohort; aging driver; biological age; coagulation factor; multimodal; systemic aging; vascular aging.