Introduction

By Richard L. Sprott and Olivia M. Pereira-Smith, guest editors

Modern biological science is at an incredibly exciting crossroad. On the one hand, we have at our disposal new and enormously powerful tools that have come to us from molecular biology and molecular genetics. These tools offer us the possibility to understand and even effect basic changes in the biology of living beings. Such changes have the potential to improve the life and health of most human beings. This science, however, is seen by many as enormously dangerous. The arrogance it takes to contemplate changing the biology (altering the genome) of living creatures may not always be accompanied by the wisdom and humanity needed to choose wisely. Indeed, a significant portion of our population believes that any research in this direction is misguided. Discussions of what is genuinely scientifically desirable are rarely well presented in the popular media. Promises about dramatic increases in human lifespan, the eradication of age-related disease, and the achievement of healthy old age for everyone are usually counterpoised with horrific projections of a society bankrupted by "greedy geezers."

Aging is clearly a complex, multifactorial process. Individuals age differently. Many 90-year-olds exhibit a better aging-related healthspan and are more active than younger individuals. Genetically identical animals, reared in controlled environments, also exhibit very different mortality. Only a small number live to the "maximum" lifespan of the species. The big question is, Why are the differences in mortality and health so large for mice or men? In this issue of Generations, we have a chapter that addresses this important question. We have also attempted to highlight areas of aging research that we believe offer the greatest promise for improving the healthspan of the elderly. The population of aging individuals continues to grow in our society, and we have included chapters that address the policy and ethical issues that result from this growth.

Since aging is so complicated, scientists have attempted to design simpler model systems with which to pursue such studies. These systems include the animal models that have revealed single gene mutations that extend lifespan. The results of these studies may not be directly extrapolated to humans, but the results contribute to understanding the molecular mechanisms that could be exploited in devising interventions to address basic aging processes or age-related diseases. In a similar fashion, the cell senescence model has led to the identification of genes critical for cell cycle control and has provided a better understanding of growth regulation in normal and cancer cells. The discovery of the enzyme telomerase now allows scientists to grow important cell types in culture and then adapt them in cell transplantation and cloning of an individual's own cell in order to improve health.

Through the Human Genome Project, an international collaborative effort, the human genome is soon to be completely sequenced--which means that we will know the individual components of dna, allowing us to identify genes that are currently unknown. This exciting accomplishment will have a tremendous impact on scientific progress, but will also bring with it ethical and public policy issues and problems. It will clearly allow us to identify genes and alleles (alternate forms of genes) that affect disease, aging, and lifespan. The question will then be how to deal with this information, how to disseminate it so that it is not disruptive. If individuals wish to be tested for the presence of genetic factors that affect disease and lifespan, should this be allowed? And who will pay for what could be expensive testing? Our aim is to stimulate thought, informed discussion, and action about these various questions.

What we have tried to accomplish with this issue is a clear and reasonable presentation of what is scientifically plausible, together with discussion of the very real issues raised by this science. We hope the reader finds this collection of essays interesting and informative.