MRI-based multi-organ clocks for healthy aging and disease assessment

Area of Science:

• Biomedical Engineering
• Genetics
• Gerontology

Background:

• Biological aging clocks are crucial for understanding aging and disease.
• Existing frameworks often focus on single organs or tissues.
• There is a need for comprehensive, multi-organ aging assessment tools.

Purpose of the Study:

• To develop and validate seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs).
• To investigate the genetic and molecular underpinnings of these MRIBAGs.
• To explore the association of MRIBAGs with disease risk, mortality, and cognitive decline.

Main Methods:

• Utilized data from 313,645 individuals from the MULTI Consortium.
• Developed seven MRIBAGs using magnetic resonance imaging data.
• Performed genome-wide association studies, genetic correlation, Mendelian randomization, and multi-omics analyses.

Main Results:

• Identified 53 MRIBAG-locus pairs and supported organ-specific and cross-organ interconnections.
• Linked MRIBAGs to 2,923 plasma proteins, 327 metabolites, and 24 non-MRI aging clocks.
• Prioritized nine druggable genes for anti-aging interventions and linked MRIBAGs to disease risk and mortality.

Conclusions:

• The seven MRIBAGs provide an enhanced multi-organ biological aging framework.
• MRIBAGs demonstrate clinical potential for advancing aging research and identifying therapeutic targets.
• Brain MRIBAG profiles correlate with differential cognitive decline trajectories.