An Extracellular Matrix Aging Clock Based on Circulating Matrisome Proteins Predicts Biological Aging and Disease.

Area of Science:

• Proteomics
• Biomarkers
• Aging Research

Background:

• Plasma proteomic clocks estimate biological age and link to age-related diseases.
• Extracellular matrix (ECM) proteins are crucial for tissue structure and age-related decline.
• Limited research has focused on circulating ECM proteins as aging biomarkers.

Purpose of the Study:

• To profile plasma ECM protein abundances across the human lifespan.
• To develop an ECM-based aging clock for predicting chronological age.
• To investigate the potential of ECM proteins as biomarkers for aging and disease.

Main Methods:

• Utilized publicly available proteomic datasets.
• Analyzed plasma ECM protein abundances across different age groups.
• Constructed and validated an ECM-based aging clock using 14 plasma proteins.
• Performed cross-species comparisons and explored drug targets.

Main Results:

• Identified a U-shaped trajectory for plasma ECM protein abundance with age.
• Developed an ECM aging clock that accurately predicts chronological age across validations and biofluids.
• Demonstrated the clock's ability to distinguish between healthy and diseased states.
• Showed that species-specific ECM clocks track aging and can be reversed by rejuvenation interventions.

Conclusions:

• Circulating ECM proteins are sensitive biomarkers of aging and disease.
• An ECM-based aging clock offers a robust measure of biological age.
• Targeting ECM remodeling presents potential strategies for promoting healthy aging.