ILAR Journal 38(3) 1997

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ILAR Journal 38(3)
Animal Models of Aging Research

Introduction
Richard L. Sprott and Robert J. Russell

Living longer--but will we prosper and enjoy it more? Are longer lives necessarily better lives? Our quest to avoid growing old dates back to the visits of Ponce de León as he searched the New World for the Fountain of Youth.

During the past few decades, a dramatic shift in the number of aged individuals has occurred in many populations around the world. Improvements in the environment, nutrition, public hygiene, and disease control procedures have greatly contributed to both the absolute and the proportionate expansion of our graying population. A steady drop in birth rates has also occurred as has an increase in worldwide longevity.

At the time of this writing, individuals throughout the world can expect to live 65 years or more. This is in contrast to those alive at the beginning of the first millennium, when people usually died in their early 20s. In 1900, the US life expectancy was 51 years for females and 48 years for males. By 1990, the life span had increased by 28 years for women and 24 years for men.¹ This new order, consisting of a burgeoning aging population and a proportionally decreasing number of younger individuals, will significantly challenge our worldwide medical, social, and political institutions.

Growing older is not in itself a satisfactory goal unless a productive, full, healthy quality of life is also maintained. To further improve the quality of life, continued progress in our understanding of aging processes is necessary. We need definitive answers to such questions as What causes aging? How is the rate of aging determined?

Numerous aspects of phenotype and genotype are implicated in limiting life span. The ethical, informed, and optimal use of animal models is absolutely required to help define the changes that occur during aging processes and to assist in the development of methods and interventions that will retain and improve the quality of human life, thereby increasing the "health span" of individual members of the species.

In this issue of ILAR Journal, each individual article provides a broad overview of select animal models that have made and will continue to make major contributions to our understanding of aging and our ability to modulate the human aging processes that have come from some animal models--senescence-accelerated mice (Takeda and others), other rodent models (McClearn; Richardson and others; Sprott and Ramirez), and birds and small nonhuman primates (Austad). The information gathered from the animal models outlined in the 6 articles in this issue will help increase our understanding of the aging process and thereby help reduce the financial and social burdens of aging on our worldwide society. This information will help permit individuals to live well and longer, suffering fewer health problems as they live full, productive lives.

As noted by Drs. Sprott and Ramirez, rats and mice are the species of choice for most animal aging studies. Most rodents used in aging studies must be cared for and maintained for 3 or more years, therefore requiring considerable financial investment. However, senescence-accelerated mice (SAM) undergo significant aging changes by the age of 6 months and have been under development by Dr. Takeda and others since 1970. Using genetic selection for senescence, Dr. Takeda and colleagues have developed several lines of mice that are senescence-prone and several lines that are senescence-resistant. These strains were developed based on grading scores for senescence, life span, and pathologic phenotypes; their importance as aging models is described in this article. Dr. McClearn examines the value of sampling the totality of genetic information available within a species (in this case, Mus musculus), using standardized genetically heterogeneous stocks in special breeding crosses to evaluate potential behavioral and physiologic biomarkers of aging. He also explores advancements in our ability to genetically engineer mice, wherein specific genes can be added or deleted for studying the effects of these altered genes on aging.

Dr. Richardson and colleagues note the importance of animal models, also stressing the complexity of whole animal studies used in aging or age-related disease processes. It is often difficult to establish cause-effect relationships between expression of a gene and phenotypic/physiologic changes due to inherent compensation mechanisms for genetic change and the potential effects of insertion of genes on the expression of endogenous genes.

Dr. Austad's article describes why birds, with an average longevity that is 2 to 3 times that of mammals with equivalent body mass an especially effective mechanisms for protecting against the accumulations of oxidative damage, make good animal models. He also discusses the study of small nonhuman primates, who have a closer evolutionary relationship to people than birds. The advantages of smaller monkeys over the larger nonhuman primates are that they reach sexual maturity relatively quickly, reproduce readily, and are less costly to house and maintain than the larger species of primates; yet they still provide the genetic similarities to humans that the nonprimates cannot.

The use of animal models in well-designed, controlled research projects will continue to provide valuable information on aging. The articles in this issue describe models that will help us understand how to help individuals live healthier, longer, and productive lives and to assist society in understanding what is necessary to increase life span without decreasing the quality of life.

¹US Department of Commerce. 1992. An Aging World II. In: US Bureau of Census International Population reports. Washington, DC: GPO. p 25, 92-93.