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|   | *This staff working paper was discussed at the Council's March             2003 meeting. It was prepared by staff solely to aid discussion,             and does not represent the official views of the Council or of the             United States Government.*
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.
 			_______________			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. 
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.  
Ramsey, J., et al., "Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study", Exp Gerontol  35 (9-10) (2000):1131-49. 
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. 
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.
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.)
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)
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.
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. |