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CREATING VERY OLD PEOPLE:
We are in the midst of an age of fantastic discoveries. The life span at the beginning of the 20th century was about 49 years. As we enter the 21st century, in countries like the United States, it is approaching 80 years. What if, by the end of this century we could more than double average life span to between 160 and 180 years? Impossible, you say. Think again. A concerted scientific attack on the aging process has already well underway. The world population is now more than six billion people. If the scientific endeavors are successful, as they are likely to be, potentially, at the dawn of the next century or the one after that, there could be four or five people on this planet for every one we have now, and more than one-half the population could be over 65 years, or even over 80 years, of age. Given that possibility, these are the issues that should be thoroughly discussed and debated. 1. At what point is the number of people so large that it exceeds the carrying capacity of the planet, thus sowing the seeds for our own destruction? 2. At what point does the crush of human numbers make life miserable for the vast majority of humans and impossible for many other species? 3. What will the quality of life be for very old people? 4. Will changing the boundaries of aging be accompanied by health or will certain tissues and organs deteriorate even as life span is markedly prolonged? If you live 140 years, what will happen to your hearing, sight, mental function, musculoskeletal function? 5. Will we be expected to work, support ourselves, and pay taxes until age 80, or 90, or 110 or older? 6. What percentage of us will outlive our resources and spend our extended years living in poverty? 7. Will not having huge numbers of people over age 60, with limited and often inadequate incomes if they stop working, create intense adversarial relations between younger and older persons as they compete for limited jobs and resources? 8. In the United States, at present, 13 percent of the population (over age 65) consume more than 30 percent of health care dollars. What happens when the majority is over age 65? Over age 80? Over age 100? 9. What happens to a nation when more than one-half of its people are more than 80 or 100 years old? Is it able to compete with nations with much younger populations that presumably will have greater per person productivity. 10. Above all, the overriding question - where is the research on aging going, where do we want it to go, and what limitations, if any, do we want to impose on it? Those focused on prolonging life spans once adulthood has been reached can be arbitrarily divided into two groups: those attempting to allow individuals to live their maximal life spans within current physiologic and biochemical boundaries and those who are determined to actually change the boundaries of aging. The former, in general, intend to achieve their goals by controlling major diseases (such as cancer and coronary heart disease) or by reducing some of the decrements accompanying the aging process that can promote certain diseases (for example, using nutritional supplements to slow or reverse the decline in our immune systems that characterizes the aging process). If the goals of preventing or ameliorating disease are achieved, thereby permitting individuals to live until their biologic time clocks in essence turn off physiologic and biochemical processes that sustain life, we might anticipate that life expectancy at birth would increase to perhaps 100 to 110 years (even to 120 years), roughly a three to four decade increase for the "developed" world (average life span currently 76 years) and a four to five decade increase for the "less developed" world (average life span currently 66 years). In contrast, those who would change the boundaries, view aging as a disease in itself. Scientists and non-scientists now talk of average life expectancies of 120 years to 180 years. Indeed, there are now articles and books on optional dying. This used to be the stuff of science fiction. That is no longer the case. There are multiple promising approaches to changing the boundaries of aging, including: administration of pharmacologic agents; use of an enzyme, telomerase; control of oxidant stress (free radicals) by antioxidants; and finding genes that are responsible for either aging or prolonged survivorship. In each of our cells at the end of the chromosomes are sticky areas called telomeres. These telomeres control cell life; the more often the cells divide, the shorter the telomeres get. Eventually, the telomere shortening results in cells being unable to divide and they die. The telomeres appear to serve as the biologic time clock that determines our maximum physiologic life span. If the enzyme telomerase is added to cells in the test tube, it prevents telomere shortening and the result is cells that, in essence, stay young and keep dividing, potentially indefinitely. So, the telomere fantasy is that, at appropriate intervals during our adults lives, we will drink a telomerase cocktail, the telomerase will miraculously go to all our cells, keep them young - and we will live for an incredibly long time. A decade ago, the general thinking was that aging was such a complex phenomenon that multiple interacting genes would be involved and we would be unlikely to find single controlling genes that could be manipulated. That notion has changed dramatically. In one form of premature aging, called Werner syndrome, characterized by very early hair loss, cataracts, blood vessel calcification, coronary heart disease, diabetes, and cancers, a single gene mutation appears to be responsible for the disease manifestations, death occurring at an average age of 47 years. Naturally-occurring mutations of single genes called age-1 and daf-2 result in an extraordinary prolongation of life span in earthworms. A variety of other single gene candidates are now being investigated that may control critical pathways or may be the controlling factor in a cascade of events that define the aging process. If single genes can be found that play a controlling or dominant role in the aging process, their proteins can be characterized and, with our pharmaceutical cornucopia, pharmacologic agents can be created that either mimic gene products considered desirable or interfere with gene products that are considered undesirable. Genetic manipulation to control oxidant stress has already produced marked prolongation of life in fruit flies and reducing the number of calories in the diet has resulted in similar extension of life in mice and rats. It now appears that the extension of life span in calorically-restricted rodents may be related to the behavior of a single gene called SIR-2. In this regard, a recent study on fruit flies found that slight modification of a single gene called Indy (standing for I'm not dead yet) doubled life span. The gene, also present in humans, appeared to work by changing metabolism so that the fruit flies ate normally, but behaved as if they had their caloric intake reduced; they appeared to be using energy differently. Importantly, these fruit flies, like calorically-restricted mice and rats, appeared to retain their vitality and normal function, even with extended life spans; they were actually able to reproduce for a longer time than normal fruit flies. The senior investigator on that extraordinary study, Dr Stephen Helfand, is quoted as saying that eventually "it may be possible to design a drug that can extend life". The drug he envisions would also be used to prevent or treat obesity, so it would be very widely used. Some urge us not to worry about moving the boundaries of aging because these "very old" fruit flies, earthworms, and rodents are at least as "healthy" as their younger counterparts. But, at this early stage in the research, such conclusions are very premature - and what happens in mice, rats or fruit flies may not apply to humans. Furthermore, what if these glib optimists, whose statements are based on no human experience, are wrong? We would then have unstoppable technologies that create huge numbers of very, very old people who will cause extraordinary family and societal physical, emotional, and economic burdens. The critical point is that there is now a concerted attack not only on diseases and abnormalities accompanying chronological aging, but also on the aging process itself. The scientific advances in this area are stunning and progress in both areas (maximizing physiologic life span and changing the boundaries of aging) is so spectacular that the possibility for human application of these animal, insect, and test tube studies in the not-too-distant future by responsible scientists and physicians is very real. Already, as expected, enthusiastic, often irresponsible, entrepreneurs are hawking to the gullible various pharmacologic antidotes to aging. If we are able to delay death markedly by creating average life spans of 120, 140, 160, or 180 years, there will inevitably be a lot more people living on planet Earth at any given time. How many might there be? Surprisingly, the demographers have, thus far, virtually ignored the technologic achievements and consequent possibility of profound extension of life spans. I have been unable to find any relevant published projections that focus on this issue. The population experts all use maximal average life spans of less than 100 years. That is scary. Uncertain as such projections may be, we need them to guide discussions and public policy. I asked Robbert Associates Ltd of Ottawa, Canada, a futures-oriented company, to use their "what if" software program to provide information on world population in the year 2100 if life expectancy increased to an average of 90 years by the year 2040 (a two decade increase in life expectancy). Their model projects a 2.5 billion person increase for every ten-year increase in life expectancy. Using different assumptions for ultimate world population projections, an expert demographer at the International Program Center of the U.S. Census Bureau estimated a 1.3 billion person increase in eventual world population for every decade increase in average life expectancy from 90 to 120 years. Using those two projections - 1.3 to 2.5 billion increase in eventual world population for every decade increase in average life expectancy, the following would be the anticipated world population as life expectancy increases beyond 80 years: Average Life Expectancy
Eventual Population Obviously, catastrophic events, such as hundreds of millions or billions of deaths from emerging disease epidemics, bioterrorism, nuclear war, or other overwhelming events could modify these projections. The calculations are also based on equal longevity increases around the world. That, of course, would not happen initially. The life span prolongation will first take place in the "developed" world (Europe, North America) where the technologies are likely to be available earlier. Asia and Latin America would be expected to follow in a matter of decades. In Africa, where the aging of the population is occurring much more slowly, the emphasis will continue to be largely on reducing infant mortality; technologies to markedly prolong life spans will probably be utilized much later. Whatever the sequence of adoption of life extending technologies, whatever calculations and assumptions are used, marked extension of life span would have a profound effect on world population. At some point, population growth and population size are likely to have substantial adverse effects on the planet and its inhabitants (Table 1). The potential negative effects of population growth are magnified by global warming. Indeed, the two are inextricably interconnected. The greater the number of people on the planet, the more severe the global warming because at least some portion of global warming is man made. On the other hand, global warming accentuates many of the problems created by excessive population growth. For example, there are currently about 40 million persons who are either refugees outside their own countries or internally displaced. In a world hotter by several degrees centigrade and with a population of 10 billion or more, the devastating effects of floods, drought, and wars could create hundreds of millions of refugees and internally displaced persons. That would, most likely, create a situation beyond our coping capacity. Surely common sense would suggest that excessive population growth is very likely to have some very unpleasant consequences, and that the health and prosperity of humankind, as well as other creatures that share the planet with us, is likely to require that population be stabilized at some reasonable level (say 10 to 12 billion persons). If that notion is accepted, then it follows that the greatest threat to achieving population stability at reasonable levels will not be a failure to control birth rates, but rather the extension of adult life span. That, in turn, invites the conclusion that the greatest threat to planetary stability is within the scientific community. Some forty years ago, Archibald MacLeish, in an extraordinary essay titled "Master or Man", noted (minimally modified to put it in the present tense) "the loyalty of science is not to humanity, but to truth - its own truth - and the law of science is not the law of the good - what humanity thinks of moral, decent, humane - but the law of the possible. What it is possible for science to know, science must know. What it is possible for technology to do, technology will have done". We were then and are now even more in an era of scientific domination - a period of unfettered technology that has and will produce many stunning discoveries that will benefit mankind, but some that are likely to harm our global society. In the same essay, MacLeish quotes the celebrated scientist-author-philosopher Rene Dubos as saying at an international conference "we must not ask where science and technology are taking us, but rather how we can manage science and technology so they can help us get where we want to go". Where is the evidence we are following Dubos' admonition and first figuring out where we want to go, rather than reacting some time in the future to the consequences of scientific discoveries that lengthen life spans profoundly? The answer is nowhere! For starters, we need biologic scientists, ethicists, philosophers, demographers, theologians, historians, economists, politicians, social scientists, psychologists, among others, to become a lot more interested in the potential consequences of our astounding and accelerating technologic achievements in the area of aging. I would submit that we need to create thoughtful guidelines. We need to initiate thorough discussions both inside and outside the scientific community. We need to establish sensible regulations, and even laws, consistent with goals defined after vigorous debate and analysis. If we do not do this, the consequences of the technologic and scientific achievements that markedly lengthen adult life spans will be imposed upon us. That could be a very unpleasant scenario. I would suggest that we concentrate on conquering diseases and slowing the aging process so people can live out their maximal physiologic life span. That will benefit individuals; it will simultaneously challenge the global society as average life expectancy increases by 20 or 30 years, but with a reasonable amount of thought and planning, we can cope with those changes. On the other hand, we should approach changing the boundaries of aging with great caution, insisting on debating the questions I posed at the beginning of this essay and requiring that any attempt to change the boundaries in human beings be kept experimental and be accompanied by rigorous long-term assessment that includes evaluating the quality of life of these very old persons. In sum, my view is: Maximizing physiologic life span - full speed ahead. Changing the boundaries of human aging - go slow with extreme caution. The research into aging is spectacular, but the implications and potential consequences are so profound that we cannot afford to leave it solely in the hands of the scientific community. We had better figure out where we are going or we may find some unpleasant surprises when we get there. Let the debate begin.
TABLE 1 Greater likelihood
of global warming
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