We are pleased to share a remarkable research advance led by our council member, Professor Guang-Hui Liu. On May 8, 2026, his team published the study “Multimodal clocks of human aging” in Cell. This work establishes a quantifiable, simulatable and intervenable digital human framework for aging research, delivering a systematic solution to assess biological age, resolve organ aging heterogeneity and identify actionable aging intervention targets.

A Multicenter Standardized Cohort and Three-Tiered Aging Clock System

The research team built the mCAS (multicentric Chinese aging standardized cohort) encompassing 2,019 healthy individuals aged from 18 to 91 across four clinical centers. By integrating over 240 clinical physiological parameters together with multi-layered molecular phenotypes including epigenome, transcriptome, proteome, metabolome, metagenome and single-cell transcriptome datasets, the researchers constructed three complementary aging clock modules.

The core capacity clock quantifies the progressive decline of overall physiological function. Powered by deep learning algorithms, the multimodal clock fuses multi-omics data and achieves a mean absolute error of merely 3.87 years in biological age prediction. The organ-specific aging clocks, developed via liquid biopsy approaches, enable independent evaluation of biological age for six major organs: brain, liver, lung, muscle, blood vessel and skin. The results reveal organ-specific aging trajectories: the liver reaches its aging inflection point at around 40 years old, notably earlier than the brain at approximately 50 years old. Two distinct phases of accelerated aging are also identified, namely 40–50 years and 60–70 years of age.

Coagulation Factors: Functional Drivers of Multi-Organ Senescence

Moving beyond conventional correlational analysis, the study further uncovers causal mechanisms of aging. Multiple coagulation factors show progressive upregulation throughout the aging process, and these factors are mainly secreted by senescent liver cells.

A series of functional experiments verify their key role in driving aging. In vitro assays confirm that these coagulation factors directly induce senescent phenotypes in human aortic endothelial cells. In vivo animal experiments demonstrate that elevated F13B, a key coagulation factor, triggers accelerated senescence and inflammatory infiltration across multiple mouse tissues. These findings prove that plasma coagulation factors are not just incidental biomarkers, but core molecular drivers that induce aging in blood vessels and other organs.

Promising Clinical Translation for Precision Aging Assessment and Intervention

This research brings tangible value to clinical application. A panel of roughly 100 plasma proteins can effectively reconstruct both core capacity clocks and organ-specific clocks, suggesting routine blood tests can serve as a convenient tool to evaluate individual biological age. Organ-resolved aging clocks support early detection of prematurely aged organs, extending the time window for early screening and diagnosis of aging-related disorders.

Lifestyle analysis indicates that earlier bedtime, moderate walking and regular fruit intake are closely associated with slowed biological aging. The team also identified multiple proteins with causal links to aging-related diseases, which provide promising candidates for therapeutic development.

Relevance for the scientific mission of π-HuB

Decoding the human proteome across the full life cycle stands as a core scientific mission of π-HuB. Focusing on the aging phase of human life, this study offers a practical and referable implementation pathway for related work within the initiative.

The research adopts large-scale standardized cohort design, multi-omics integration and artificial intelligence modeling to characterize aging processes, and effectively distinguishes correlational molecular markers from causal functional drivers. These approaches and findings deliver valuable insights for exploring protein functions and dynamic proteome changes during physiological and pathological progression. Furthermore, its translational workflow from fundamental discovery to clinical application also provides meaningful references for advancing proteomics research and related translational studies across π-HuB.