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Liver- and Immune-Enriched Molecular Signatures Associated With Mortality in Older Adults
Yi-Long Huang1, Wei-Ju Lee1,2,3, Pei-Lin Lee1
1Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Aging Cell
|July 15, 2026
Summary
Plasma proteomics and metabolomics can predict mortality risk in older adults. A 20-protein score outperformed clinical factors, identifying key biological pathways linked to aging and mortality.
Area of Science:
- Gerontology and Aging Research
- Biomarker Discovery
- Molecular Biology
Background:
- Quantifying biological aging necessitates biomarkers reflecting multisystem decline beyond chronological age.
- Understanding molecular underpinnings of mortality risk is crucial for interventions.
Purpose of the Study:
- Compare prognostic performance of plasma proteomics, metabolomics, and clinical factors for all-cause mortality.
- Characterize molecular pathways linked to mortality risk and age-related decline.
Main Methods:
- Untargeted plasma proteomics and metabolomics in 848 adults (I-Lan Longitudinal Aging Study).
- Cox proportional hazards models for mortality-associated features and pathways.
- Elastic net regression for omics-based mortality risk scores, validated externally.
Main Results:
- 79 mortality-associated proteins identified (predominantly liver- and immune-related).
- Pathway analysis revealed dysregulation in coagulation, complement, oxidative stress, glucose, and bile acid metabolism.
- A 20-protein score showed strong discrimination (C-index 0.81), outperforming metabolite (0.77) and clinical (0.73) models.
Conclusions:
- Plasma multi-omics profiling is a scalable tool for biological age assessment.
- Liver- and immune-enriched signatures are associated with mortality risk in older adults.
- Identified pathways may inform interventions for aging and functional decline.
