Читать книгу Aging - Harry R. Moody - Страница 89

Leonard Hayflick

The premise upon which the following ideas rest is that the survival of a species depends upon a sufficient number of its members reaching sexual maturation and producing enough progeny that reach independence to guarantee the continuation of the species. Natural selection, guided by beneficial mutations, has molded the biology and the survival strategies of all living things to achieve this fundamental goal. As previously indicated, the best strategy to guarantee that an animal or human will survive long enough to mature sexually is to provide it with more than the minimum required capacity in its vital organs. In this way, if damage or pathology occurs in an essential system before sexual maturation, there is a greater likelihood that the animal will still survive to reproduce and pass on to its progeny its superior physiological capacity. This general strategy, essential for the survival of all species, has evolved in different ways for various life forms. Energy and purpose are concentrated to achieve reproductive success, which assures the immortality of the genes. The continuation of the germ line is the driving force of natural selection. Longevity of individual animals is of secondary importance.

Animals are selected through evolution for having physiological reserves greater than the minimum necessary to reach sexual maturation and rear progeny to independence, but once this critical goal has been attained, they have sufficient excess reserve capacity to “coast” for a period of time, the remainder of which we call their life span. This time period, then, is indirectly determined genetically. During the coasting period the animal functions on its excess capacity. This physiological reserve of energy and functional capacity does not renew at the same rate that it incurs losses, so molecular disorder—entropy—increases. Random changes or errors appear in previously well-ordered molecules, resulting in the normal physiological losses that we call age changes. These changes increase the vulnerability of the animal or human to predation, accidents, or disease (Holiday, 2004).

What happens after reproductive success and raising progeny to independence is not important for the survival of a species. What happens next, of course, is aging and, ultimately, death. Wild animals, because they rarely live long enough, do not experience aging. The entire scenario is analogous to the ticking on of a cheap watch after the guarantee period has ended. The watch’s guarantee period corresponds to the time spent by animals to reach sexual maturation and to finish rearing progeny. After the warranty period ends, the watch does not simply “die” because it would be prohibitively expensive to put a mechanism in a cheap watch that would cause it to self-destruct on the day after the guarantee expires. Likewise, it would cost too much of energy to make a system in an animal that would cause it to die precisely on the day that its progeny become independent. What happens after the guarantee period expires in watches and after the reproductive period in animals is aging, which inexorably leads to failure in watches and death in animals.

In this way of thinking, survival to sexual maturation is accomplished by postponing until after reproductive maturity the effects of genes that perform well in youth but become mischief-makers later. When these once good, now harmful genes eventually do switch on, they provide the blueprint for age changes….

Until now we have almost always thought about aging by asking, “Why do we age?” And biogerontologists have designed their experiments to attempt to answer this question. The results have not been impressive. With the exception of the discovery that age changes occur within individual cells, we do not know much more today about the fundamental cause of aging than we did a century ago. Most of what we have learned is descriptive: we know much more about what happens than we did before but very little about why it happens. Biogerontologists have described changes that occur as we age from the molecular level up to the level of the whole animal. However, these descriptive observations add little to our understanding of the basic process.

It is for this reason that George Sacher proposed that we have been asking the wrong question. Instead of asking “Why do we age?” we should ask “Why do we live as long as we do?” By asking that question we might reorder our thinking and be able to design experiments to obtain more fundamental information. I think this is a useful new approach and I hope that more biogerontologists will come to appreciate the subtle but important reason for asking this better question.

Implicit in the question “Why do we live as long as we do?” is the idea that our longevity has increased and may be capable of increasing further. That appears to be true, since the human life span is known to have increased since prehistoric times. If our life span has increased, then it is likely that the start of the aging process has changed within the new time frame. Based on this reasoning, we may conclude that the aging process is malleable, that we can understand how it occurs, and that perhaps we can tamper with it….

I do not believe that we have a sufficient understanding of either the aging process or the determinants of life span to expect to significantly manipulate either during our lifetime. A more important issue, however, is whether it would be desirable to manipulate either process. The capacity to halt or slow the aging process, or to extend longevity, would have consequences unlike most other biomedical breakthroughs. Virtually all other biomedical goals have an indisputably positive value. It is not at all clear whether or not the ability to tamper with the processes that age us or determine our life span would be an unmixed blessing. As pointed out earlier, resolution of all disease and other causes of death would result in a life expectation of about one hundred years. I am apprehensive about extending average life expectation beyond age one hundred once the leading killers are resolved because the result would be disease-free but nonetheless functionally weaker, still inexorably aging people….

Virtually all biomedical research has the implicit goal of eliminating disease in all of its forms. It is logical to ask what will happen if we are successful. The answer seems to be that if we are successful, our life expectation will be increased but we will eventually die from the basic aging processes that lead to failure in some vital system.

Source: “Why Do We Live as Long as We Do?” from How and Why We Age by Leonard Hayflick, PhD. Copyright ©1994 by Cell Associates, Inc. Foreword copyright © 1994 by Robert N. Butler, MD. Reprinted by permission of Leonard Hayflick, PhD.