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The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents
P M Treuting1, J M Snyder2, Y Ikeno3
1Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA treuting@uw.edu.
Abstract:
Pathology is a discipline of medicine that adds great benefit to aging studies of rodents by integrating in vivo, biochemical, and molecular data. It is not possible to diagnose systemic illness, comorbidities, and proximate causes of death in aging studies without the morphologic context provided by histopathology. To date, many rodent aging studies do not utilize end points supported by systematic necropsy and histopathology, which leaves studies incomplete, contradictory, and difficult to interpret. As in traditional toxicity studies, if the effect of a drug, dietary treatment, or altered gene expression on aging is to be studied, systematic pathology analysis must be included to determine the causes of age-related illness, moribundity, and death. In this Commentary, the authors discuss the factors that should be considered in the design of aging studies in mice, with the inclusion of robust pathology practices modified after those developed by toxicologic and discovery research pathologists. Investigators in the field of aging must consider the use of histopathology in their rodent aging studies in this era of integrative and preclinical geriatric science (geroscience).
Insights
Histopathology is crucial for accurate rodent aging studies, providing essential context for diagnosing causes of death and age-related diseases. Integrating systematic pathology ensures complete and interpretable research in geroscience.
Area of Science:
- Gerontology
- Comparative Pathology
- Biomedical Research
Background:
- Pathology integrates diverse data in aging studies.
- Histopathology provides essential morphologic context for diagnosing illness and causes of death in aging rodents.
- Many current rodent aging studies lack systematic necropsy and histopathology, leading to incomplete and contradictory findings.
Purpose of the Study:
- To emphasize the critical role of systematic pathology in rodent aging research.
- To advocate for the integration of robust pathology practices in aging study designs.
- To highlight the necessity of histopathology for interpreting age-related outcomes.
Main Methods:
- Discussion of factors for designing aging studies with pathology integration.
- Adaptation of toxicologic and discovery research pathology practices for aging studies.
- Emphasis on systematic necropsy and histopathology as essential endpoints.
Main Results:
- Aging studies without systematic pathology are incomplete and difficult to interpret.
- Systematic pathology analysis is required to determine causes of age-related illness, moribundity, and death.
- Histopathology is vital for understanding the effects of interventions like drugs, diets, or gene alterations on aging.
Conclusions:
- Histopathology is indispensable for comprehensive rodent aging studies.
- Integrating pathology enhances the reliability and interpretability of geroscience research.
- Investigators must incorporate robust pathology practices into aging study designs for accurate preclinical geriatric science.

