Circulating protein signatures enriched in liver and immune markers predict all-cause mortality in older adults with superior performance to conventional clinical risk factors. A 20-protein score achieved C-index 0.81 for mortality discrimination and validated consistently across independent cohorts, establishing plasma proteomics as a scalable biomarker platform for biological age stratification.
Key Points
- Liver-derived and immune proteins predict mortality better than clinical factors
- Dysregulation spans coagulation, complement, oxidative stress, glucose metabolism
- 20-protein score outperforms metabolite models and traditional risk assessment
Longevity Analysis
This research demonstrates that multisystem physiological decline manifests as coordinated dysregulation across distinct molecular pathways—coagulation cascades, inflammatory responses, metabolic control, and antioxidant capacity—rather than isolated biomarker elevations. The liver-enriched signature suggests that hepatic synthetic and metabolic function represents a critical node in aging physiology; when these functions degrade, systemic risk escalates markedly. The superior predictive power of proteomics over individual clinical measures indicates that capturing the body's integrated communication network provides more actionable information than snapshot measurements. This approach fundamentally shifts how practitioners can interpret aging: rather than treating chronological age as destiny, plasma protein profiles expose which individuals have accumulated the greatest multisystem burden and thus warrant more intensive intervention strategies targeting the specific pathways involved
Original published by Wiley Aging Cell, by Yi‐Long Huang, Wei‐Ju Lee, Pei‐Lin Lee, Li‐Ning Peng, Fei‐Yuan Hsiao, Liang‐Kung Chen .