Plasma Metabolomic Signature Predicting Deviation from Healthy Vascular Aging in Two European Cohorts

Area of Science:

• Cardiovascular Science
• Metabolomics
• Aging Research

Background:

• Biological age, distinct from chronological age, is a key determinant of healthy aging.
• Cardiovascular diseases remain a leading cause of morbidity and mortality, necessitating improved risk prediction.
• Plasma metabolomic profiles offer potential biomarkers for age-related health trajectories.

Purpose of the Study:

• To identify a plasma metabolomic signature predictive of age-related cardiovascular risk (pMTB-age).
• To assess the association of this signature with vascular morbidity and mortality.
• To explore the role of specific metabolites and pathways in vascular aging.

Main Methods:

• Utilized nuclear magnetic resonance (NMR) spectroscopy to analyze plasma metabolites in discovery (Flemish) and replication (Spanish) cohorts.
• Developed a predictive model (pMTB-age) using elastic net regression relating chronological age to plasma metabolome.
• Employed SHapley Additive exPlanations (SHAP) for metabolite importance and pathway analysis.

Main Results:

• A 18-metabolite signature (pMTB-age) was identified, explaining significant variance in chronological age.
• pMTB-age and its C-age-uncorrelated component (pMTB-age-R) were associated with cardiovascular risk factors and mortality.
• Pathway analysis revealed overrepresentation of glycine, serine, and threonine metabolism.

Conclusions:

• pMTB-age serves as a multidimensional biomarker for accelerated vascular aging.
• The signature precisely identifies individuals at high cardiovascular risk.
• pMTB-age can inform personalized prevention and treatment strategies for vascular disease.