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Updated: Oct 5, 2025
The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
Published on: July 24, 2018
PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging
Shabnam Salimi1, Christina Pettan-Brewer2, Warren Ladiges2
1Department of Epidemiology and Public Health, University of Maryland Baltimore, School of Medicine, Baltimore, MD, USA.
Background:
Multimorbidity is a public health concern and an essential component of aging and healthspan but understudied because investigative tools are lacking that can be translatable to capture similarities and differences of the aging process across species and variability between individuals and individual organs.
Methods:
To help address this need, body organ disease number (BODN) borrowed from human studies was applied to C57BL/6 (B6) and CB6F1 mouse strains at 8, 16, 24, and 32 months of age, as a measure of systems morbidity based on pathology lesions to develop a mouse PathoClock resembling clinically-based Body Clock in humans, using Bayesian inference. A mouse PhysioClock was also developed based on measures of physiological domains including cardiovascular, neuromuscular, and cognitive function in the same two mouse strains so that alignment with BODN was predictable.
Results:
Between- and within-age variabilities in PathoClock and PhysioClock, as well as between-strain variabilities. Both PathoClock and PhysioClock correlated with chronological age more strongly in CB6F1 than C57BL/6. Prediction models were then developed, designated as PathoAge and PhysioAge, using regression models of pathology and physiology measures on chronological age. PathoAge better predicted chronological age than PhysioAge as the predicted chronological and observed chronological age for PhysioAge were complex rather than linear.
Conclusion:
PathoClock and PhathoAge can be used to capture biological changes that predict BODN, a metric developed in humans, and compare multimorbidity across species. These mouse clocks are potential translational tools that could be used in aging intervention studies.
Insights
Researchers developed a mouse PathoClock and PhysioClock to measure aging and multimorbidity. The PathoClock, based on pathology, better predicted chronological age than the PhysioClock, offering translational tools for aging studies.
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.
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