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Updated: Mar 23, 2026
Modeling Age-Associated Neurodegenerative Diseases in Caenorhabditis elegans
Published on: August 15, 2020
Models for preclinical studies in aging-related disorders: One is not for all
Gaetano Santulli1, Consuelo Borras2, Jean Bousquet3
1Department of Physiology and Cellular Biophysics, Columbia University Medical Center; College of Physicians & Surgeons, New York, USA;
Abstract:
Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment-effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical.
Insights
Selecting appropriate animal models is crucial for reliable preclinical studies. Well-justified models minimize bias, improving the generalizability of treatment effects to human subjects, especially in aging research.
Area of Science:
- Preclinical research
- Translational medicine
- Aging research
Background:
- Preclinical studies utilize animal models to investigate disease mechanisms and treatment efficacy.
- Generalizing findings from animal models to human subjects is a key objective.
- Challenges exist in preclinical research due to potential biases, such as experimenter expectations and model-specific responses.
Purpose of the Study:
- To underscore the importance of selecting appropriate and validated animal models in preclinical research.
- To highlight how model selection impacts the reliability and generalizability of study outcomes.
- To address specific challenges in aging research where human studies are often impractical.
Main Methods:
- Review of factors influencing the reliability of preclinical efficacy studies.
- Discussion on the impact of model selection on causal inference.
- Consideration of bias in outcome assessment and strain-specific responses in animal models.
Main Results:
- Inappropriate model selection can introduce bias and limit the generalizability of findings.
- Experimenter expectations and strain-specific responses can confound results.
- Well-justified model systems are essential for robust preclinical data.
Conclusions:
- The careful selection of animal models is paramount for valid preclinical research.
- Addressing model-related biases enhances the translational potential of findings.
- Validated model systems are critical for advancing our understanding of diseases, particularly in aging.
