Introduction

Powerful molecular biological tools have begun to open up the very fabric of life—the human genome—and have allowed us to glimpse inside this Pandora's box. We now see that many common disorders of later life—for example, cancer, dementia, and vascular disease—are related to genetic variations that dictate an individual's likelihood of developing illnesses like these. These genetic variations differ from those that determine longevity, though both act synergistically to dictate how long and how well we might live. Control of gene expression will be needed to counteract the adverse actions of these to promote a healthy and productive old age.

Aging and disease—separate entities or continuum of change?

Common disorders such as cardiovascular disease, cancer, stroke, dementia, and diabetes become increasingly prevalent in later life. It is tempting to ascribe these to the body “wearing out”—a viewpoint supported by the frequent finding in many old, but otherwise healthy, people of low levels of the same kind of tissue changes generally associated with certain diseases when present in higher amounts. These diseases have been popularly equated with “normal aging,” and the idea that in diseased individuals this normal process of aging may have become “exaggerated” or have “accelerated” out of control has often been put forward.

Health and disease might in this way be thought of as occupying a sliding scale of age determined tissue damage, with the one merging into the other at some point in life. Yet the argument is fallacious. Many disorders—for example, dementia—clearly become more common in later life; their incidence peaks in people in their eighties but then declines.1 Furthermore, like humans, other animals (including the higher primates) age and die, yet they do not spontaneously develop these common disorders of humans. Hence, although growing older is a biological certitude, disease in old age may represent an additional burden of tissue damage superimposed …