第五章：寿命的遗传学

In Chapter 3, we established the theoretical basis of how genes selected for their impact on survival to reproductive age (that is, on fitness) also determine longevity, and we showed how mathematical theories and empirical laboratory research have demonstrated the “fixing” of genes that delay the start of reproduction, which increases longevity. We did not, however, discuss which genes and/or genetic pathways are involved in increasing longevity. In this chapter we take a closer look at some specific genes and genetic pathways that can alter life span.

Our exploration into the genetic basis of longevity focuses primarily on genes and pathways for which a general consensus has been established, arrived at through repeated experimentation. Keep in mind, as you read through this chapter, that our knowledge comes largely from studies on three simple, short-lived organisms—a yeast, a worm, and a fly—that are raised and studied under highly controlled laboratory conditions. Although at least 200 genes have been identified as having some impact on the rate of aging and longevity, only a handful of these have been studied in sufficient detail to be presented here. And although we can demonstrate that the manipulation of specific genes can affect longevity, it is important to remember that all genes have been selected for their ability to enhance survival to reproductive age, not for longevity. That is, genes are fixed because they provide a reproductive advantage, not because they increase the longevity of the species.

We begin with a review of gene expression and its regulation in eukaryotes, then briefly describe some of the methods used to analyze gene expression. Then we look at some specific genes and genetic pathways that affect longevity in Saccharomyces cerevisiae (a yeast), Caenorhabditis elegans (a roundworm), Drosophila melanogaster (fruitfly), and Mus musculus (mouse).