Theories Of Aging And Life Extension

Theory without fact is fantasy, but fact without theory is chaos. C. O. Whitman (1894)

An old adage says that nothing is certain except death and taxes. That is true, but it does not say anything about four score being the absolute measure of a person's years. That is good because knowledge about the biology of aging is changing, and with it people's expectations of what they can do about it. This new knowledge and the likely uses people will make of it will challenge perceptions of what constitutes a full human life as well as force people to rethink the increasing ability to alter aging. However, it is necessary here to define what is being talked about. What exactly do people mean when they talk about aging and senescence, and what is known about how aging comes about?

One goal of the material that follows is to answer the first question briefly in modern biological terms. Another goal is to describe the current understanding of the biological mechanisms that underlie aging. The final goal is to review successful cases of longevity intervention in laboratory animals and discuss their implications for humans. More extensive details and references on these general topics can be found in Arking (1998), Masoro and Austad (2001), and the Science of Aging-Knowledge Environment website.

The twenty-first century is forecast to be "the century of biology." Not only has the genome of many organisms been sequenced, scientific understanding of the way in which a fertilized egg transforms itself into a complex multicellular organism has taken giant strides to the point where developmental biology in the twenty-first century is taught as a complex series of gene-environment interactions. An outcome of these investigations has been the realization that there are few truly different developmental mechanisms. Apparently disparate organisms such as flies and humans use the same basic mechanisms in somewhat different ways. The modular nature of living organisms makes it possible to translate findings obtained with one species (e.g., flies or worms) to another species (e.g., humans). However, the adult that arises from this developmental process goes on to age and senesce and die. Somehow the sophisticated interactions fail to keep working. This seems paradoxical. As the Nobel laureate Francois Jacob wrote, "It is truly amazing that a complex organism, formed through an extraordinarily intricate process of morphogenesis, should be unable to perform the much simpler task of merely maintaining what already exists" (1982, p. 50).

Jacob's paradox contains two different questions. The first is the longtime philosophical poser: Why do people age? The second is the mechanistic consideration: How do people age? In the terminology of Ernest Mayr, the first component addresses the nature of the ultimate processes and the second addresses the details of the proximate mechanisms. Therefore, the answer to Jacob's paradox must be bipartite because the understanding of the mechanistic processes of aging depends crucially on an understanding of the evolutionary rationale for aging.

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