PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging

Area of Science:

• Gerontology
• Comparative biology
• Biomedical research

Background:

• Multimorbidity is a significant public health issue in aging populations.
• Current investigative tools lack translatability for comparing aging processes across species and individuals.
• There's a need for better tools to study aging and healthspan variability.

Purpose of the Study:

• To develop and validate mouse models for assessing aging and multimorbidity.
• To create a mouse PathoClock and PhysioClock analogous to human clinical Body Clocks.
• To enable cross-species comparisons of aging and identify potential intervention targets.

Main Methods:

• Applied body organ disease number (BODN) to C57BL/6 and CB6F1 mice across different ages.
• Developed a mouse PathoClock using Bayesian inference on pathology lesions.
• Created a mouse PhysioClock based on cardiovascular, neuromuscular, and cognitive functions.

Main Results:

• Observed significant between- and within-age variabilities in PathoClock and PhysioClock.
• Both clocks correlated with chronological age, with stronger correlations in CB6F1 mice.
• Developed PathoAge and PhysioAge prediction models; PathoAge demonstrated superior prediction of chronological age.

Conclusions:

• Mouse PathoClock and PhysioClock can capture biological changes predicting multimorbidity.
• These models facilitate cross-species comparisons of aging and disease burden.
• The developed mouse clocks serve as potential translational tools for aging intervention studies.