Aged Rodents for Biogerontology Research

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Nancy L. Nadon

Studies in animal models have provided much of our understanding of the changes that occur in normal aging and in age-related diseases that humans encounter in their journey through life. Even lower organisms such as flies and worms have contributed to our understanding of human aging. But the rodent has been the most valuable model for biogerontology research because of the similarity between rodent physiology and that of humans and the low cost to maintain them. This chapter will discuss the advantages of the rodent model for aging research, provide some examples of the types of investigations made possible with the rodent model, discuss the special issues and concerns to be considered when using aged rodents, and describe resources available to facilitate studies with rodents.


Human aging is the result of a complex interaction between biological changes and environmental/social influences. Healthcare throughout life, diet, and habits such as smoking, alcohol consumption and physical activity can all impact the rate of biological aging and complicate the study of the biology of aging in human populations. The rodent provides a venue for modeling the biological changes with age and investigating the genetic and physiological basis of aging and age-related diseases while controlling intrinsic and extrinsic influences. The genetic background, diet, environment, and health status of the rodent can be strictly controlled. Rodents are similar to humans in much of their physiology, cellular function, and to a lesser degree, even their anatomy. The musculoskeletal system, immune and endocrine systems, and gastrointestinal tract are very similar in both function and architecture between rodents and humans. Cardiac function has been modeled in rodents, as have age-related changes in the liver. While the rodent brain is more primitive than the human brain on the organ level, at the cellular level there are many similarities between rodent and human central nervous systems that can be exploited.

Rodents provide a good model for testing potential therapeutics, combining the value of a mammalian system with a low-cost test subject. Longitudinal studies are more feasible in a short-lived rodent model than in a human population. The ability to analyze tissue at all stages of the process, be it normal aging or disease development, is one of the major benefits of working with the rodent model. In addition, the rodent model is amenable to manipulation at the genetic level, allowing us to test the role of gene products and pathways in age-related changes.

An example of an area of current emphasis where the rodent has made a vital contribution is the interaction of obesity with normal aging and age-related diseases. Obesity has become a serious public health concern—one that is the product of both biological and environmental/ social contributions. It is a polygenic trait, with multiple genetic pathways contributing to the phenotype. Rodent studies allow for the dissection of the genetic contributions and the role of the environmental/behavioral contributions, and also the testing of potential therapeutic interventions. Many chromosomal regions (quantitative trait loci or QTL) have been identified as influencing obesity, and each contributes only a small percent of the overall phenotype (reviewed in Brockmann and Bevova, 2002). There are not only additive effects of different genes but also gene-gene interactions and geneenvironment interactions, demonstrating the complexity of this phenotype.

Insulin resistance is a problem common to aging and obesity, and there are strain differences that can be exploited for studies in rodent models. Figure 33.1 compares the insulin resistance response to a high-fat diet in DBA/2J and C3H/HeJ mice, illustrating not only strain differences but also gender differences in the response by DBA/2J mice.

There are also many mutant and genetically engineered rodent models that address one or more aspects of obesity and the role of insulin resistance in aging, reviewed elsewhere (Tschop and Heiman, 2001; Mauvais-Jarvis et al., 2002; Carroll et al., 2004). One mutant mouse model of obesity, the leptin-deficient (ob/ob) mouse, exhibits obesity and increased insulin resistance. When leptin deficiency (ob/ob) was combined with the knockout of the adipocyte fatty acid binding protein aP2 gene,

Handbook of Models for Human Aging

Copyright © 2006 by Academic Press All rights of reproduction in any form reserved.

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