Introduction

A useful approach to the introduction of any book about the biology of aging (after first clarifying the essential terminology) is to consider three traditional questions that have always driven biogerontological research. In keeping with that philosophy, we first shall give a brief summary of what can be referred to as senescent phenotypes (What is aging?). We will conclude that there is a remarkable range of senescent phenotypes that impact physiological functions at all levels of analysis and in all body systems. Next, we will consider what is surely the most fundamental of all gerontological questions (Why do we age?). The evolutionary biological theory of why aging occurs remains by far the most satisfying explanation, although there have been certain challenges to that idea. Finally, we will very briefly introduce the third—and by far the most difficult—question, one to which the modern tools of molecular biology and genetics have only recently begun to be successfully applied (How do we age?).

There is little doubt that genomic instability—the theme of this book—is a major pathway toward senescent phenotypes, particularly of the numerous neo-plastic proliferations that emerge during the last half of the life spans of mammalian species. The mitochondrial genome and the nuclear genome are important targets of such instability. A recent surprise is the evidence that mitochondrial dysfunction also may participate in the pathogenesis of disorders of proliferative homeostasis, probably including atrophies as well as hyperplasias, as they are among the cell's generators of signals to implement apoptosis (1,2). The equations that ensure a healthy, steady state of cell numbers within our various tissues include factors for the determination of cell death as well as cell birth. Mitochondria are important generators of signals that lead cells to commit suicide; the alterations of such signals by dysfunctional mitochondria may thus alter the balance of these equations.

These components of DNA damage are not likely to be the only pathways modulating life span and the rates of development of senescent phenotypes. Several other classes of gene action can contribute to the pathobiology of aging, including those that modulate posttranslational alterations to proteins, such as gly-cations (3).

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