Staff Working Paper

Age-Retardation: Scientific Possibilities and moral challenges

The inevitability of aging, and with it the specter of dying, has always haunted human life; and the desire to overcome age, and even to defy death, has long been a human dream. Many of the oldest human stories are myths of long lives: of ancients who lived for hundreds of years, of far-away places where even now the barriers of age are broken, or of magical formulas, concoctions or fountains of youth. And the goal of conquering aging was not confined to magic and myth; it was central to the aspirations of the founders of modern science, who sought through their project the possibility of mastering nature for the relief of the human condition—decay and death emphatically included. But it is only more recently that modern biotechnology has actually been put to work in this quest for youth and longevity, and some of its results of late seem genuinely promising.

The retardation of aging is among the most complex—both scientifically and ethically—of the potential “non-therapeutic” uses of biotechnology, involving several different scientific avenues, and raising deeply complicated questions for individuals and society. The case for living longer hardly needs to be made, and the desire to live longer speaks powerfully to each and every one of us. But the full consequences of doing so may not be quite so obvious.

Basic Terms and Concepts
Though everybody more or less knows what aging means, offering a concrete definition is no simple task. In one sense, aging just refers to the passage of time in relation to us or, put another way, it describes our passage through time. The more years we have lived, the greater our age (and with it our cumulative experience of life). In this sense, of course, it is absurd to speak of age-retardation for, by definition, only death could put a stop to our increasing years. But we mean more than this by “aging.” It encompasses not only the passage of time but also (and more so) the biological processes that accompany that passage, and especially the progressive degeneration that affects the body and mind, beginning in adulthood. To clarify the discussion that follows, we offer some basic definitions for aging and related terms:

Aging: In this paper we shall use “aging” synonymously with “senescence,” rather than merely to describe the number of years a person has been alive. Aging therefore denotes the gradual and progressive loss of function over time, beginning in adulthood, leading to decreasing health and well-being, increasing vulnerability to disease and increased likelihood of death.

Age-Retardation: the slowing down of the processes involved in aging, and therefore the stretching of the aging process over a greater number of years, resulting in delayed decline and degeneration and very likely also a longer life. It is one form of life-extension.

Life-Extension: An increase in the number of years that a person remains alive. It may be accomplished by a variety of means, including the slowing down of aging, combating the diseases of the aged, or reducing causes of death among the young. It may involve pushing back senescence or merely allowing an individual to survive into longer and deeper senescence.

Lifespan: The verified age at death of an individual, and therefore the strictly chronological duration of life.

Maximum Lifespan: The longest lifespan ever recorded for a species—in humans today it is 122.5 years.

Life Expectancy: The average number of years of life remaining for individuals at a given age, assuming that age-specific mortality risks remain unchanged.

Life Cycle: The series of stages through which one passes in the course of life—including, among others, infancy, childhood, adolescence, adulthood, and decline; and the overall form given to the experience of life by the relations of these stages and the transitions between them.

A few further clarifications of these terms and their uses are in order. First, this paper addresses the subject of age-retardation, as opposed to the larger subject of life-extension. Life-extension may take three broad forms: 1) allowing more individuals to live to old age by combating the causes of death among the young and middle-aged; 2) further extending the lives of those who already live to advanced ages by reducing the incidence and severity of diseases and impairments of the elderly or by replacing cells, tissues and organs damaged over time; and 3) age retardation which would slow the general process of aging.

The first, particularly in the form of combating infant mortality (mostly through improvements in basic public health, sanitation and immunization), is largely responsible for the great increase in life expectancy in the 20th century, from an average life expectancy at birth of about 48 years in 1900 to an average of about 78 years in 1999 in the United States. But this approach has been so successful that almost no further gains in average life expectancy can be expected from efforts to improve the health of the young. In fact, even if, starting today, no one in the United States died before the age of 50, average life expectancy at birth would increase by only about 3.5 years. The increasing lifespans of the 20th century were an extraordinary achievement, but further significant gains in life expectancy would require a much greater feat: extending the lives of older people.

The second approach, which would extend the life of the elderly by combating particular causes of death or reversing some of the damage done by senescence, has been most actively pursued over the past several decades. In some forms, it has already contributed to the improved health of the elderly and to moderate extensions of life. Extreme old age already is, in many respects, a work of art, and modern medicine seems likely to make it more so and to bring further modest increases in average lifespan. But this approach, too, promises relatively moderate (though surely meaningful) lifeextension, even if it succeeds far beyond the most optimistic of present expectations.

For instance, if diabetes, all cardiovascular diseases, and all forms of cancer were eliminated today, life expectancy at birth in the United States would rise to about 90 years, from the present 78. This would certainly be a significant increase, but not one so great as to bring about many of the social and moral consequences that might be anticipated with significant age-retardation. It would be a much smaller increase than that achieved in the last century. Also, it would likely not have a serious impact on the maximum lifespan. More importantly, since this approach does not get at the more general physical and mental deterioration that often comes with old age, and which we more generally think of as “aging,” it would allow individuals to live longer, but often thereby expose them further and for a longer time to the other ravages of the general process of progressive degeneration, including loss of strength, hampered mobility, memory problems, impairments of the senses and declining mental functions. Extensions of life that do not address this general degeneration consign their beneficiaries to the fate of Tithonus or the Struldbruggs in Swift’s Gulliver’s Travels: degeneration without end. A number of the most promising avenues of cutting-edge aging research—including those involving stem cell research, tissue and organ replacement and, potentially someday, nanotechnology—would likely fall into this category. Promising though these may be, their presently foreseeable applications do not seem likely to significantly extend the maximum human lifespan or to fundamentally alter the shape of the human life cycle. Discussion of these techniques will therefore be limited.

It is the third approach—direct age-retardation, now being actively pursued on several paths—that, if successful, promises the most significant and meaningful changes, physical, social, and moral. This paper will restrict its discussion largely to age-retardation, its possible scientific forms and potential consequences. If successful, age-retardation would not only extend the average lifespan, it would extend the maximum lifespan, and perhaps quite significantly, and it may involve heretofore unknown changes throughout the human life-cycle.

Scientific Background
The concept of age-retardation presumes the existence of a general organism-wide process of aging, as opposed to a series of unconnected processes of degeneration which must be treated individually. For aging as a whole to be slowed, there must be such a thing as “aging as a whole.” Biologists have debated the existence of such a unified process of senescence for many years, but over the last two decades experimental evidence has increasingly suggested that it does indeed exist. There is still no clear empirically supported theoretical concept of just how aging works, but the evidence has shown that a number of techniques appear to affect the aging of a wide variety, if not indeed all, of the body’s organs and systems. Sharp decreases in caloric intake, and a number of genetic interventions in animals (both of which will be discussed in greater detail below) have been shown to have dramatic effects not only on longevity, but on practically every measurable expression of the rate of aging, including the rates of memory loss, muscle loss, declining activity, immune system response, and a broad range of bodily processes that might not otherwise be conceived of as synchronized.

Even if the way in which these techniques of age-retardation work is not fully understood, it seems increasingly likely that there is in fact a single process of aging on which they do their work, and that most if not all of the various phenomena of aging are deeply connected and, in principle, could be jointly influenced by certain sorts of interventions. It seems increasingly likely, therefore, that something like age-retardation is in fact possible.

The most prominent techniques of age-retardation currently under investigation fall into the following four general categories:

1. Caloric Restriction: It has been known since the mid-1930s that substantial reductions in the food intake of many animals (combined with nutritional supplements to avoid malnutrition) can have a dramatic effect on lifespan. With nearly seven decades of laboratory research, this is by far the most studied and best-described avenue of age-retardation, though scientists still lack a clear understanding of the mechanism by which it operates. What is clear, however, from numerous studies in both invertebrates and vertebrates (including mammals), is that a reduction of food intake to about 60 percent of normal has a significant impact not only on lifespan, but on the rate of decline of the animal’s neurological activity, muscle functions, immune response and nearly every other measurable marker of aging. Moreover, it is now clear that the effect is not a product of a diminished metabolism, as was long believed. Caloric-restricted animals do become physically smaller, but they process energy at the same levels as members of their species on a normal diet. In fact, studies in mice and rats suggest that caloric restriction appears to result in significantly increased rates of spontaneous activity, including the ability to run greater distances and to maintain a “youthful” level of activity at an age well beyond that of non-restricted animals of the same species. (Importantly, however, caloric-restriction also often results in sterility, or reduced fertility in animals.)

The degree of life-extension (and likely age-retardation) achieved through caloric-restriction is quite remarkable. In mice and rats, researchers have regularly found lifespan extended by over 30 percent, and in some studies over 50 percent.¹ Studies have also found significant extensions of life, and signs of retarded aging in a number of other mammalian species, including recently a 16 percent increase in the lifespan of dogs.²

Studies of caloric restriction in monkeys, conducted since the late 1980s at the National Institute on Aging, the University of Maryland, and the University of Wisconsin, have shown comparable effects even on some of our nearest evolutionary cousins.³ Caloric-restricted monkeys have been shown to retain youthful levels of several vital hormones well into late-adulthood, have lower blood pressure and, over a 15-year period, suffer substantially less chronic illness than members of their species on normal diets. The effect on lifespan is as yet not known. Monkeys generally live several decades, so it will be years before it is apparent whether caloric-restricted monkeys live significantly longer than others.

The biological basis for the dramatic effects of caloric-restriction is not presently well understood, in large part because of the sheer number of changes wrought by a simple reduction in food intake. Hundreds of discretely measurable physiological changes occur in mice and rats on reduced diets, making cause and effect difficult to disentangle, and the process from which age-retardation results difficult to identify. However, researchers in the field believe that a number of new tools and techniques available only in the last decade or so (including DNA micro-arrays, new types of genetically engineered mice, and others) promise to facilitate a greater understanding of this process, and they believe that, in the foreseeable future, the mechanisms by which it operates might be understood, and techniques for achieving the same ends without a diet of near-starvation may be developed.

2. Genetic manipulations: Some of the most startling and extraordinary discoveries in age-retardation research have involved genetic mutations that have significant impact on lifespan and on the rate of degeneration. Over the past several decades, researchers have identified single gene alterations that, in a number of species, dramatically extend life. Such relatively simple alterations allow scientists to trace the biochemical pathways responsible for changes in the aging rate with some precision. In recent years, a surprisingly high number of such pathways have been found in nematode worms—it appears that changes in any one of at least 50 and potentially as many as 200 genes in worms can significantly extend life. Even more remarkably, at least 6 such genes have already been identified in mice, whose genetics and physiology are far more complex than those of worms. As long as life-extending single-gene mutations were restricted to worms and fruit-flies, there seemed little obvious reason to expect that they might also exist in humans. But findings that similar biochemical pathways are responsible for this phenomenon in both worms and mice suggest the potential for a similar possibility in humans. For instance, in worms, flies and mice, an alteration in an insulin-like growth factor receptor (present also in humans) has resulted in substantial increases in lifespan, suggesting the possibility that there may indeed be highly conserved general mechanisms across species, and that single-gene alterations that extend life may ultimately be discovered in humans.

Most remarkable is the magnitude of life-extension which these mutations seem to offer. In worms, where the effect has been most dramatic, a single-gene alteration has been shown to double lifespan, and an alteration in two genes has nearly tripled it. In the most extreme cases, involving particular single-gene mutations in male worms, researchers have observed a six-fold increase in lifespan. There are, of course, enormous physiological differences between humans and worms. Most notably, the cells of nematode worms do not continue dividing in adulthood, which of course has great significance for aging. In mammals, most notably mice, the effects have been less pronounced, but still quite significant. Increases of lifespan by 25 percent to even 50 percent have been reported, and single-gene mutations combined with caloric restriction have been shown to result in a nearly 75 percent increase in lifespan. That 75 percent extension is, to date, the greatest increased lifespan achieved in mammals.⁴

These single-gene mutations do, however, have serious side effects, including, most commonly, sterility or reduced fertility—problems also observed with other techniques of age-retardation. Some single-gene differences have also been shown to actually decrease longevity in one sex of a species (most notably in fruit flies, though more recently also in mice) while increasing it in the other. In addition, almost all of these mutations result in reduced body size, and increased susceptibility to cold. They also seem to reduce the animal’s ability to compete for mates, so that in experiments in which the single-gene mutation animals are placed together with normal members of their species and allowed to reproduce freely, the single-gene difference is fairly quickly selected out of the population. This may explain why such genes have never been identified in natural populations.

Single-gene differences that affect lifespan have not been studied as extensively as caloric restriction. It is not yet clear, in this case, whether what is involved is true age-retardation or a form of more general extension of life. The evidence that does exist, however, suggests a retardation of aging, and a slowing of the loss of function and the deterioration of tissues and cells.

3. Prevention of oxidative damage: For many years, there has been ample (if indirect) evidence that oxygen free radicals— molecules that have one unpaired electron, and which are therefore chemically very active—produced as inevitable consequences of the body’s various functions, cause gradual deterioration of many of the body’s cells and tissues. They can disrupt protein synthesis and repair (especially in mitochondria), and can cause minor errors in DNA replication that accumulate over time. Our body produces, or obtains through our diet, a number of anti-oxidants (such as superoxide dismutase (SOD), catalase (CAT), vitamin E, vitamin C, coenzyme Q10, and alpha lipoic acid) that destroy many, but not all, of these oxygen free radicals. The balance of oxygen free radicals and antioxidants seems, empirically and intuitively, to be connected to the rate of degeneration of cells and tissues in the body. In fact, anti-oxidants may be deeply involved in the operation of the other successful age-retardation techniques in animals. For instance it appears the balance between free radical production and antioxidant activity may modulate the impact of caloric restriction; and one specific antioxidant seems critical in the operation of nearly all the single-gene life-extending mutations in nematode worms. In addition, a recent study has shown that a synthetic antioxidant can significantly extend the lifespan of mice, and the life-extending effect of antioxidant activity in fruit flies has also been well documented. Researchers are exploring the potential for employing both naturally occurring and synthetic antioxidants in humans, to retard the degeneration of cells, reduce and slow the accumulation of errors in DNA replication, thereby extend the human lifespan, perhaps significantly. The study of free radical activity will also likely inform our understanding of the operation of other age-retardation techniques.

4. Methods of treating the ailments of the aged that might affect age-retardation: A number of techniques which do not themselves fall squarely under the heading of age-retardation may nonetheless offer vital clues to the nature of the aging process, and may have a significant role to play in the operation of age-retardation techniques. These include:

a) Hormone Treatments: It has long been known that endocrine factors are closely tied to a number of the most prominent elements of aging. The rates of production of certain hormones (particularly testosterone and estrogen) decline sharply in one’s later years, and these declines are closely related to the loss of muscle mass that accompanies aging, and a series of other age-related declines. In the past 15 years, researchers have been investigating the possibility of slowing or, in certain instances, reversing these effects of aging by the replenishment of certain hormones to more youthful levels, with particular focus on human Growth Hormone, Dehydroepiandrosterone (or DHEA), Testosterone, Estrogen, Pregnenolone, Progesterone, and Melatonin. One prominent study, conducted in 1990 and repeated several times since, showed that men between the ages of 60 and 80 who were injected with human Growth Hormone over a six-month period experienced increased muscle mass, a loss of fat, improved skin elasticity, and decreased cholesterol levels.⁵ Several animal studies using DHEA have shown substantial increases in lifespan (up to 40 percent in mice), though to this point there has been no verifiable claim of changes in human lifespans as a result of hormone replacement. This technique in a certain sense falls between what we have called age-retardation and what might be better understood as a treatment of the symptoms of aging. The human Growth Hormone studies cited above, and most similar efforts, do not appear to slow the general rate of degeneration and loss of function, but they reverse some of their particular effects, on both body and mind. Although the impact of such treatments does not appear to be generalized throughout the body, hormone treatments may play an important role in unlocking the secrets of the aging process, and in future age-retardation techniques. (The same may be said of stem cell treatments, and other forms of regenerative medicine.)

b) Telomere Research: Since the mid-1980s, researchers have known that telomeres—which form the tips of chromosomes—shorten over time, as cells divide, and that eventually this causes cells to stop dividing and to die. Certain cells—germ cells, cancer cells, some stem cells, hair follicles and others—are able to escape this process of degeneration with the help of an enzyme called telomerase, that slows the erosion and shortening of telomeres. Several studies in the 1990s suggested that telomere length correlates with cell aging, so that preventing the shortening of telomeres can slow the aging of cells, and, under certain conditions, might do so without increasing the risk of uncontrolled cell-growth and cancers.⁶ The links between cell-aging and the general aging of organisms are, however, still quite unclear. A number of particular conditions of the aged—including wrinkling of the skin, age-related muscular degeneration, and atherosclerosis—have been linked, in various degrees, to cellular aging and degeneration, and recent work by French researchers has suggested a link between hypertension and accelerated cell aging. These studies suggest a use for the manipulation of telomeres in counteracting and even preventing certain “symptoms” of aging, but at this point no convincing link has been demonstrated between telomere length and the general process of organismic senescence. The appearance of changes in telomere length in experiments with other age-retardation techniques, including caloric restriction and single-gene mutation, suggests a potential connection, but for the moment the nature of that connection remains unclear. The promise of telomere manipulation appears greatest as a means of combating some afflictions of the aged, rather than retarding aging as such.

These different avenues of age-retardation research are not as clearly distinguished from one another as this classification suggests. In almost all cases, the employment of one technique offers results that are relevant for the understanding of the others. Caloric restriction seems to affect antioxidant production; genetic alterations affect telomere length. Several of these methods have also been shown to work in tandem. Also, recent developments and advances in the tools of cellular and molecular biology have begun to fuse together these disparate fields. The techniques used for one are often also used in the others.

None of these techniques have been demonstrated to increase human lifespans or to slow the process of aging in humans. Such a demonstration would be quite difficult to undertake, since the human lifespan is on average between six and eight decades, and assessing effects on it would require a great deal of time, and more than one generation of researchers (as the subjects outlived the researchers). But animal experiments, and the existence of analogous systems and processes in humans, suggest that scientists may indeed be able to retard the human aging process and significantly extend the maximum and average human lifespan in the foreseeable future.

Ethical Issues
That this prospect will be welcomed seems almost self-evident. Who among us would not want more healthy years added to his or her life? No one truly relishes the thought of bodily degeneration or decline, and of one’s final years marked, as Shakespeare so well put it, by “a moist eye, a dry hand, a yellow cheek, a white beard, a decreasing leg, an increasing belly…your voice broken, your wind short, your chin double, your wit single, and every part about you blasted with antiquity.” We would probably all want to save ourselves, and even more so our loved ones, from the fate we have seen some of our elders endure. The case in favor of living longer—a moral case, to be sure—hardly needs to be made in detail, and if our analysis focuses on potential drawbacks more than on potential advantages, it is not because such advantages are lacking, but rather precisely because they are so clear and powerful.

And yet, a profound alteration of the human life-cycle is certain to have serious consequences beyond the mere extension of life, and to raise difficult moral and ethical questions. Whether these questions should lead us to rethink the wisdom of the enterprise is far from clear, but at the very least we must grant them our most serious attention.

In suggesting some of these questions, we make two assumptions: 1) that technology will be available to significantly retard the process of aging, of both body and mind, and 2) that this technology will be widely available, and widely used. If the first is correct, the second almost certainly will be.

We divide our discussion of the moral questions into two sections, dealing with the effects on individuals and the effects on society and its institutions. As will become evident, however, the distinction between them is not always clear.

1) Effects on the Individual

The question of the effect of age-retardation on our individual lives must begin with a sense of what aging means in those lives.

First we must remember that aging is not just about old age. It is the life-long process by which we reach old age and the end of our lives. Accordingly, its product is not so much old age and death as the life cycle itself: the form and contour of our life in time. Aging defines youth almost as much as it does old age, because in both cases we are defined by our stage of life relative to other stages. Age-retardation would therefore affect not only our later years, but all of our years, in both immediate and mediated ways. For one thing, age-retardation might quite directly affect our youth by slowing down the processes of bodily and psychic maturation throughout life. This depends on the particular technique sought for age-retardation. An intervention made only at a later stage of life might not (biologically) affect development in earlier stages, but any of the methods that rely upon an alteration at the outset—including genetic manipulation or life-long caloric restriction mimetics—would retard aging in the young just as in the old.⁷ It could stretch out the entire life cycle, as one stretches a rubber band, extending the period we spend in infancy, childhood, adolescence, in our prime and in decline, and profoundly altering our sense of the relation between years lived and stages of life. Slower biological aging (particularly in a culture of faster “social aging” like ours, in which children are increasingly exposed to things that might not so long ago have been deemed exclusively appropriate for adult life) may cause an increasing disjunction between the maturity of the body and mind and the expectations and requirements of life.

Even if the effect is not directly biological, the retardation of aging, and with it the extension of life, would very likely affect the attitudes of the young along with those of the old. Indeed, in this sense age-retardation may affect the young far more than the old, since the attitudes of the young are shaped by a sense of what is to come, and what is to be expected of life. The great changes in average life expectancy over the 20th century have already influenced ways in which people perceive their own future. And the prospect of lives that are significantly longer than those we know today would very likely do so as well, perhaps giving rise to unprecedented sorts of expectations should the lifespan increase very markedly.⁸

How might such expectations be different? To answer this question, we must keep in mind two concepts. First is the significance of the life cycle as a whole. The language of the boosters of age-retardation research suggests an image of life as a time-line, rather than a curve with a particular shape. This implies an understanding (informed by the vocabulary and worldview of modern science) of life as composed of interchangeable and essentially identical units of time, rather than composing a whole with a meaningful form of its own. Viewed through the prism of this chronological atomism, the prospect of adding more years to our lives means simply having more years, more of the same. And since life is good, more life is better. But life as lived and experienced does not present itself homogeneously and in discreet uniform bits. The shape of the whole affects how we live every portion, and altering the shape of that whole might therefore have far greater consequences than merely giving us more time.

Second is the relation between aging and death, and between age-retardation and our attitudes about mortality. Life-extension does not mean immortality, to be sure—if for no other reason than that it is scientifically implausible. But the impulse to extend our lives in general, rather than to combat particular diseases or ailments that shorten our lives, is a declaration of opposition to death as such. In addressing aging as a disease to be cured, we are, in principle, expressing a desire never to grow old and die, or, in a word, a desire for immortality. There is no reason to suspect that life-extension research would stop once we have achieved a human lifespan of 150, or 180, or 200 years. Why would it? Having declared that our present term of life is inadequate, why should we settle for another? A life lived from the start under the influence of age-retarding techniques is a life lived in express opposition to the constraints of mortality. The underlying impulse driving age-retardation research is, at least implicitly, a desire for immortality.

These two premises are of course closely tied, since the boundaries and shape of the life cycle give form and possible meaning to a mortal life. Its virtue is not so much in that it leads us to death, but in that it reminds us, by its very nature, that we will someday die, and that we must live in a way that takes heed of that reality. If we remained at our prime, in full swing, for decade after decade, and even for centuries, the character of our attitudes and our activities would likely change significantly. These changes may take at least five principal forms:

1. Commitment and engagement: Our activities are all, in one way or another, informed by the knowledge that we have only a limited portion of years to use up. Knowing that, we seek to spend our lives in the ways we deem most important and vital to us. The notion of spending a life suggests a finite quantity of available devotion, and as any economist knows, the scarcity of a commodity contributes to its value. The very experience of spending a life, and of becoming spent in doing so—that is, the experience of aging—contributes to our sense of accomplishment and commitment, and to our sense of the meaningfulness of the passage of time, and of our passage through it. Being “used up” by our activities reinforces our sense of fully living in the world. Our dedication to our activities, our engagement with life’s callings, and our continuing interest in our projects all rely to some degree upon a sense that we are giving of ourselves, in a process destined to result in our own end. A life lived devoid of that sense, or so thoroughly removed from it as to be in practice devoid of it, might well be a life of lesser engagements and weakened commitments—a life other than the one that we have come to understand as fully human. This is not to say it will be worse—but it will very likely be quite different.

2. Aspiration and urgency: Very much related to our sense of being used up in the course of our lives is the sense of urgency given to life by the prospect of foreseeable death. This may be what the Psalmist is getting at when he asks God to “teach us to number our days, that we may get a heart of wisdom.” Many of our greatest accomplishments are pushed along, if only subtly and implicitly, by the spur of our finitude and the sense of having only a limited time. A far more distant horizon, a sense of essentially limitless time, might leave us less inclined to act with some urgency. Why not leave for tomorrow what you might do today, if there are endless tomorrows before you? Our sense of the size and shape of our future—our “life expectancy”—greatly affects how we act and think in the present.

3. Renewal and children: Perhaps most significant, and most intriguing, is the deep connection between death and new birth. The link between longevity and fertility is a nexus of profound and mysterious human significance. The link seems inescapable, and appears again and again, in different forms and different arenas, both in empirical scientific investigation, and in any effort at moral analysis. Most of the age-retardation techniques tested in animals to this point appear to result in very significant decreases in fertility. Various theories have been proffered to explain this link, mostly having to do with a relationship between the mechanisms that enable fertility and those that result in degeneration and death. Some have even suggested that the changes connected to puberty may well be linked to those that trigger decline. Fertility and aging appear to be biologically linked. Moreover, they seem to be linked in terms of human behavior and experience. Throughout the 20th century, increases in life expectancy have been accompanied by decreases in the birth rate.⁹ Of course, increased longevity alone does not explain declining birthrates, but surely it is an element of the broader cultural transformation that does explain that decline. One important reason for the apparent experiential link between longevity and childbearing seems readily intelligible: without awareness of and concern for degeneration, there is no desire for renewal. And so a world of men and women who do not feel the approach of their own decline will likely have far less interest in bearing children. Children are one answer to mortality. But people in search of other more direct and immediate answers might very well be far less welcoming of children, and far less interested in promoting human renewal through the coming of new generations.

4. Attitudes toward Death and Mortality: An individual committed to the scientific struggle against aging and decline may be the least prepared for death, and the least willing to acknowledge its inevitability. Therefore, given that these technologies would not in fact achieve immortality, but only lengthen life, they would in effect make death even less bearable, and make their beneficiaries even more terrified of it and, in a sense, obsessed with it. The fact that we might die at any time could sting far more if we were less attuned to the fact that we must die at some time. In an era of age-retardation, we might, in practice, therefore live under an even more powerful preoccupation with death, but not one that leads us to commitment, engagement, urgency and renewal.

5. The Meaning of the Life Cycle: There is also more to the question of aging than the place of death and mortality in our lives. Not just the specter of mortality, but also the process of aging itself affects our lives in profound ways. Aging, after all, is a process that mediates our passage through life, and that gives shape to our sense of the passage of time and our own maturity and relations with others. Age-retardation technologies at once both make aging more manipulable and controllable as explicitly a human project, and sever age from the moorings of nature, time, and maturity. They put it in our hands, but make it a less intelligible component of our full human life. In the end, they could leave the individual unhinged from the life-cycle. Without the guidance of our biological life-cycle, we would be hard-pressed to give form to our experiential life-cycle, and to make sense of what time, age, and change should mean to us.

Any of these effects of course would most likely be subtle, and it would be exceedingly difficult to hold them up against the promise of longer and longer life and to expect any of us simply to reject the offer. But in considering the offer, we must take into account the value inherent in the human life-cycle, in the process of aging, and in the knowledge we have of our mortality as we know it. We should recognize that age-retardation may irreparably distort these, and leave us living lives that, whatever else they might become, are in fundamental ways different from—and perhaps less rich than—what we have to this point understood to be truly human.

Powerful as some of these concerns are, however, from the point of view of the individual considered in isolation the advantages of age-retardation may well be deemed to outweigh the dangers. But individuals should not be considered in isolation, and the full potential meaning of age-retardation cannot come into view until we take in the possible consequences for society as a whole. When we do so, some of these individual concerns become far more stark and apparent, and new concerns emerge as well.

2) Effects on Society

To begin to grasp the full implications of significant age-retardation, we must imagine what our world would look like if the use of such techniques became the norm. This is both a reasonable expectation and a useful premise for analysis. If effective age-retardation technologies became available and relatively inexpensive, the vast majority of us would surely opt to use them, and they would quickly become popular and widely employed. For our analysis, moreover, viewing the effects of these technologies in the aggregate both highlights the consequences they would have for individuals by drawing them out and showing what they would mean on a large scale, and allows us to see certain consequences that affect the society and its institutions directly, and that are not just individual effects writ large.

The full social effects of age-retardation probably would not be evident until the first cohort to benefit from treatment began to cross the barrier of the present maximum lifespan, but lesser consequences would become evident much sooner, as more and more of the population survived to older ages, and lived with the plausible expectation of doing so.

Consequences will likely be apparent at every level of society, and in almost every institution. Among the more obvious may be effects on work opportunities, new hires, promotions and retirement plans; housing patterns; social and cultural attitudes and beliefs; the status of traditions; the rate and acceptability of social change; the structure of family life and relations between the generations; political priorities and choices, and the locus of rule and authority in government.

To paint a fuller picture, we might divide the potential social implications of age-retardation into three broad categories:

1. Generations and families: Family life and the relations between the generations are, quite obviously, built around the shape of the life cycle. A new generation enters the world when its parents are in their prime. With time, as parents pass the peak of their years and begin to make way and assist their children in taking on new responsibilities and powers, the children begin to enter their own age of maturity, slowly taking over and learning the ropes. In their own season, the children bring yet another generation into the world, and stand between their parents and their children, helped by the former in helping the latter. The cycle of succession proceeds, and the world is made fresh with a new generation, but is kept firmly rooted by the experience and hard-earned wisdom of the old. The neediness of the very young and the very old put roughly one generation at a time at the helm, and charge it with caring for those who are coming, and those who are going. They are given the power to command the institutions of society, but with it the responsibility for the health and continuity of those institutions. In a society reshaped by age-retardation, generation after generation would reach and remain in their prime for many decades. Sons would not surpass their fathers in vigor just as they prepared to become fathers themselves. One generation would have no obvious reason to make way for the next as the years passed. The succession of generations would be obstructed by a glut of the able. The old would think less of preparing their replacements, and the young would see before them only layers of their elders blocking the path, and no great reason to hurry in building families or careers. Families and generational institutions would surely reshape themselves to suit the new demographic form of society, but would that new shape be good for the young, the old, the familial ties that bind them, the society as a whole, or the cause of well-lived human lives?

2. Innovation and change: The same glut would likely affect other institutions, private and public. From the small business to the city council, from the military to the Fortune 500 corporation, generational succession would be disrupted, as the rationale for retirement diminished. With the slowing of succession cycles might well also come the slowing of the cycles of innovation and adaptation in these institutions. Innovation is often the function of a new generation of leaders, with new ideas to try and a different sense of the institution’s mission and environment. Waiting decades for upper management to retire would surely stifle this renewing energy and slow the pace of innovation—with costs for the institutions in question and society as a whole.

3. The Aging of Society: Even as the ravages of aging on the lives of individuals were diminished, society as a whole would age. The average age of the population would, of course, increase, and, as we have seen, the birthrate and the inflow of the young would likely decrease. The consequences of these trends are very difficult to forecast, and would depend to a great extent on the character of the technique employed to retard aging. If the delay of senescence made it more acute when it did come, then the costs of caring for the aged would not be reduced but only put off, and perhaps increased. The trend we have already seen in our society, whereby a greater share of private and public resources goes to pay for the needs of the aged and a lesser share for the needs of the young, would continue and grow. But society’s institutions could likely adapt themselves to this new dynamic (though of course the fact that we can adjust to something does not in itself settle the question of whether that something is good or bad). More important is the change in societal attitudes, and in the culture’s view of itself. Even if age-retardation actually decreased the overall cost of caring for the old, which is not unimaginable, it would still increase the age of society, affecting its views and priorities. The nation might commit less of its intellectual energy and social resources to the cause of initiating the young, and more to the cause of accommodating the old. A society is greatly strengthened by the constant task of introducing itself to new generations of members, and might be greatly weakened by the relative attenuation of that mission. A world that truly belonged to the living—who expected to exercise their ownership into an ever-expanding future—would be a very different, and perhaps a much diminished, world, focused too narrowly on maintaining life and not sufficiently broadly on building the good life. If individuals did not age, if their functions did not decline and their horizons did not narrow, it might just be that societies would age far more acutely, and would experience their own sort of senescence—a hardening of the vital social pathways, a stiffening and loss of flexibility, a setting of the ways and views, a corroding of the muscles and the sinews. This sort of decline would be far less amenable to technological solutions.

A society reshaped in these and related ways would be a very different place to live than any which we have known before, and there is much to suggest that in the terms that matter it might well be a lesser place: less accommodating of full human lives, less welcoming of new and uninitiated members, and less focused on the purposes that reach beyond survival. Aging and mortality are deeply tied to many of the best things about our lives, as individuals and as members of society, and their radical transformation must lead us to think hard about the sort of world we wish to build, or to avert.

Conclusion
The prospect of effective and significant retardation of aging—a goal we are all at first strongly inclined to welcome—is rife with barely foreseeable consequences. We have tried to gesture toward some possible effects, though no one can claim to know what a world remade by near-agelessness would really look like. The broader issue toward which these particular potential consequences seem to point has to do with the meaning of certain elements of our human experience that medical science may now allow us to alter and manipulate. The ability to retard aging puts into question the meaning of aging in our lives, and the way we ought best to regard it: Is aging a disease? Is it a condition to be treated or cured? Does that mean that all the generations that have come before us have lived a life of suffering, either waiting for a cure that never came or foolishly convincing themselves that their curse was just a blessing in disguise? Is human life, as our ancestors understood it and as our faiths and our philosophies describe it, really just a problem to be solved? The anti-aging medicine of the not-so-distant future would treat what we have usually thought of as the whole, the healthy, human life as a condition to be healed. It therefore presents us with a questionable notion both of full humanity, and of the proper ends of medicine.

It puts in stark terms the question that defines much of our larger investigation of the uses of biotechnology that go beyond the treatment of the sick and wounded: is the purpose of medicine to make us perfect, or to make us whole? The human being in his or her natural wholeness is not a perfect being, and it is that very imperfection, that never fully satisfactory relation with the world, that gives rise to our deepest longings and our greatest accomplishments. It is what reminds us that we are more than mere chemical machines or collections of parts, and yet that we are less than flawless beings, seamlessly a part of and perfectly content in a world fully under our control and direction. It is the source of what we most appreciate about ourselves.
Some foreseeable biotechnologies, like those of effective age-retardation, hold out the prospect of perfecting some among our imperfections, and must lead us to ask just what sort of project this is that we have set upon. Is the purpose of medicine, in principle, to let us live endless painless lives of perfect bliss, or is its purpose rather to let us live out the humanly full span of life within the edifying limits and constraints of humanity’s grasp and power? As that grasp grows, and that power increases, these fundamental questions of human purposes and ends become more and more important, and finding the proper ways to think about them becomes more vital but more difficult. The techniques themselves will not answer these questions for us, and ignoring the questions will not make them go away—even if we lived forever.

1. A useful review of caloric restriction work in animals is Weindruch, R, and R.L. Walford, "The retardation of aging and disease by dietary restriction", Springfield, IL: Charles Thomas Publishers, 1998.
2. The study of caloric restriction in dogs, conducted by researchers at the University of Pennsylvania, the University of Illinois, Cornell University and Michigan State University, is expected to be published in May in the Journal of the American Veterinary Medical Association. Preliminary results were announced by the University of Pennsyl-vania in September.
3. Ramsey, J., et al., "Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study", Exp Gerontol 35 (9-10) (2000):1131-49.
4. These results refer to a yet-unpublished study brought to the Council's attention by Steven Austad in his presenta-tion at the December 2002 meeting.
5. Rudman, D., et al., "Effects of human growth hormone in men over sixty years old", The New Engl J of Med 323 (July 5, 1990): 1-5.
6. An overview of the subject by Dr. Blackburn in the journal Nature from November of 2000 sheds light on this con-troversial question (Blackburn, E.H., (2000) "Telomere states and cell fates", Nature 408(6808): 53-56.)
7. Dietary effects on aging in the young, for instance, have been known for some time. A relation between diet and the age of onset of puberty in humans has been suggested by some recent studies (perhaps most notably Herman, M. et al., (2002) "Secondary Sexual Characteristics and Menses in Young Girls Seen in Office Practice: A Study from the Pediatric Research in Office Settings Network,", Pediatrics, 99: 505-512)
8. In this sense, life expectancy turns out to be uniquely useful. Life expectancy is a measurement, based on statistical tables of mortality, of the number of additional years that people of some particular age may expect to live at a given time. This may seem better suited for insurance purposes than for capturing a snapshot of longevity. And yet, life expectancy may be distinctly useful to moral reflection and analysis, because it is a measure of the number of years a person may expect to have yet ahead of him or her at any moment. It is therefore a measure of the view ahead, of the expected and anticipated years to come, which has much to do with our attitudes about aging and death. Many of the most significant consequences of age retardation would result from an increase in the number of years that peo-ple can expect to live, and from the resulting changes in attitudes.
9. Even the great "baby-boom" of the 1950s and 60s in the United States was not actually a result of substantially increased birth rates. In 1900, the birth rate was just above 30 births per thousand population; in 1950 (roughly the beginning of the period called the "baby boom") it was 24.1, and in 1965 (the end of that period) it was 18.4. It is not increased rates of child-bearing but rather extraordinary reductions in infant mortality (allowing many more children to live to adulthood) that explain the relative size of the generation born in those years. The birthrate has since continued to decline, reaching approximately 15 births per thousand population in 2001, bringing it closer to the death rate, and therefore bringing population growth roughly into line with earlier figures.