The Biology of Aging: Observations and Principles

By Robert Arking | Go to book overview

7
Genetic Determinants of
Longevity in Animal Models

7.1
Introduction

It has long been a popular axiom that our inheritance plays a major role in determining our length of life. Indeed, an apocryphal saying prescribes that, if one wishes to live a long and happy life, one should first arrange to have parents who are long-lived and wealthy. But note that this truism immediately mixes together both genes and environment, for who would doubt that wealth alters the context within which our genes interact with each other and with the environment. Successful identification of the genetic determinants of longevity thus depends to a large extent on our ability to minimize environmental effects while maximizing genetic effects. Only then can we identify which, if any, genes play a major role in significantly extending (or decreasing) longevity. The need to minimize the environmental factors means that we must deal with simple environments. We humans have constructed, live in, and interact with an incredibly rich mix of complex environments; our study must start not with us but with experimental animals in which we can rigorously control the environment so as to highlight the genetic effects. The fact that many studies on the biology of aging cannot, for obvious ethical, legal, and practical reasons, be done with human beings reinforces this emphasis.

The fact that our experimental procedures necessarily focus on accentuating genetic factors affecting longevity while simultaneously minimizing environmental ones means that only a simplistic misreading of this chapter would support an uncritical acceptance of genetic determinism (Lewontin 2000). However, what genetic analysis will unambiguously identify are the genetic and metabolic pathways involved in longevity regulation and the environmental conditions necessary for their expression. These dual and complementary sets of information are not only much more useful than the identification of any one gene, but will be absolutely critical to accurately understanding the process. We will also want to know whether any particular aging mechanism or senescent process is one which is, so to speak, either “public” (i.e., broadly conserved across phylogenetic lines including mammals and thus of general importance to the understanding of human aging) or “private” (i.e., restricted to species other than mammals and, while interesting, not likely to directly assist us in understanding human aging; Martin et al. 1996).


7.2
The Need for a Model Organism,
and the Cost

Only a few species are well suited for genetic investigations, in the sense that there are both a substantial body of knowledge regarding the organism's heredity, chromosome structure, life history, development, maturation, adult physiology, and reproduction and a stock center that maintains all the various wild-type and mutant strains. The knowledge and the mutants constitute the basic tools for a genetic investigation into aging processes. The four species that best meet

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