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Wednesday, 02 November 2005
Second Thoughts On Extending Life - Spans: Researchers are Making Great Strides in Extending the Boundaries of Human Aging


The Futurist

By Donald B. Louria

The World May Not be Ready for an End-of-Life Population Explosion.  (Statistical Data Included)  We are in the midst of an age of fantastic discoveries. The human life-span at the beginning of the twentieth century was about 49 years. At the start of the twenty-first 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?

A concerted scientific attack on the aging process is already well under way. The world population is now more than 6 billion people. At the dawn of the next century, or the one after that, if these scientific endeavors are successful, there could be four or five people on this planet for every one we have now. More than one-half the population then could be over 65 or even 80 years old.

Given that possibility, these are the issues that should be thoroughly discussed and debated:

At some point, the number of people may become so large that it exceeds the carrying capacity of the planet, making life miserable for the vast majority of humans (and impossible for many other species), even sowing the seeds for our own destruction.

The quality of life for very old people may be severely diminished if changing the boundaries of aging is not accompanied by reasonably good health. Certain tissues and organs may deteriorate even as life-span is markedly prolonged, so people may live 140 years with ever-worsening sight, hearing, mental function, and musculoskeletal function.

Meanwhile, we might be expected to work, support ourselves, and pay taxes until age 80, 90, 110, or older. Some of us will outlive our resources and spend our extended years living in poverty. This would likely create intense adversarial relations between younger and older persons as they compete for limited jobs and resources.

Thus, the overriding question is, 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?

Antiaging Forces

Health professionals focused on prolonging human life can be divided into two groups: (1) those attempting to allow individuals to live their maximum life-spans with current physiological and biochemical boundaries and (2) those who are determined to actually change the boundaries of aging.

The first group of professionals intend to achieve their goals by controlling major diseases (such as cancer and coronary heart disease) or by reducing some of the deterioration 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 biological time clocks in essence turn off physiological 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).

The second group of health professionals want to slow or halt the aging process. These scientists, as well as nonscientists, now talk of average life expectancies of 120 years to 180 years. Indeed, there are now articles and books on optional dying, and this topic is no longer science fiction. There are multiple promising approaches to changing the boundaries of aging, including administration of pharmacological agents, use of the enzyme telomerase, control of oxidant stress (free radicals) by antioxidants, and finding genes that are responsible for either aging or prolonged survivorship.

Alternatives to Death

In each of our cells, at the ends of our 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 biological clock that determines our maximum physiological life-span. If the enzyme telomerase is added to cells in the test tube, it prevents telomere shortening, so cells stay young and keep dividing, potentially indefinitely. The telomere fantasy is that, at appropriate intervals during our adult 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, researchers concurred 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, causing death 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, pharmacological 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 prolonged life in fruit flies. 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 calorie-restricted rodents may be related to the behavior of a single gene called SIR2. In this regard, a recent study of fruit flies found that slight modification of a single gene called Indy ("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.

Like calorie-restricted mice and rats, these fruit flies 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. Eventually, "it may be possible to design a drug that can extend life," says the senior investigator on that extraordinary study, Stephen Helfand of the University of Connecticut School of Medicine. 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. Furthermore, what happens in mice, rats, or fruit flies may not apply to humans. If the 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 physical, emotional, and economic burdens on families and society.

Thus, 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. Another danger has emerged, as might have been expected: Enthusiastic and often irresponsible entrepreneurs are hawking various pharmacological aging antidotes to the gullible.

How Many More People?

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, but, surprisingly, demographers have thus far virtually ignored the possibility of profound extensions of life-spans. I have been unable to find any relevant published projections that focus on this issue. The population experts all use maximum 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 future-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 10-year increase in life expectancy. Using different assumptions for ultimate world pop ulation 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-a 1.3-billion or 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         Eventual World 
Expectancy at Birth  Population 
100 years            12.6-15 billion 
120 years            15-20 billion 
140 years            17.6-25 billion 
180 years            23-35 billion 

Obviously, catastrophic events could modify these projections, such as the deaths of hundreds of millions of people from emerging disease epidemics, bioterrorism, nuclear war, or other overwhelming events. 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 (see box, "Potential Consequences of Excessive World Population Growth"). The potential negative effects of population growth are magnified by global warming. Indeed, population growth and warming are inextricably interconnected: The greater the number of people on the planet, the more severe the global warming will be, because at least some portion of global warming is man made. Global warming, in turn, exacerbates many of the problems created by excessive population growth. For example, there are currently about 40 million people 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 bill ion 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.

Common sense would suggest that excessive population growth could have some very unpleasant consequences, so ensuring the health and prosperity of humankind (as well as other creatures that share the planet with us) is likely to require us to stabilize population at some reasonable level (e.g., 10 to 12 billion people). 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 birthrates 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.

Guiding Science

Some 40 years ago, author Archibald MacLeish argued that the loyalty of science is not to humanity, but to its own truth, and that the law of science is not the law of the good but the law of the possible.

We are now more than ever in an era of scientific domination-a period of unfettered technology that has and will produce many stunning discoveries that will benefit humankind, but some that are likely to harm our global society. As philosopher-scientist Rene Dubos put it, "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." Today, there is no evidence that we are following Dubos's admonition and first figuring out where we want to go, rather than reacting sometime in the future to the consequences of scientific discoveries that lengthen life-spans profoundly

For starters, we need biologists, ethicists, philosophers, demographers, theologians, historians, and others to become a lot more interested in the potential consequences of our astounding and accelerating technological 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 vigorous debate and analysis to define our goals, and we need to establish sensible regulations and laws consistent with those goals. If we do not do this, the consequences of the technological and scientific achievements that markedly lengthen adult life-spans will be imposed upon us. That could be a very unpleasant scenario.

I suggest that we concentrate on conquering diseases and slowing the aging process so people can live out their maximum physiological life-span. That will benefit individuals. It will also challenge the global society, as average life expectancy increases by 20 or 30 years, but we can cope with those changes with a reasonable amount of thought and planning.

On the other hand, we should approach changing the boundaries of aging with great caution, insisting on debate and requiring that any attempt to change the boundaries in human beings be kept experimental. Such attempts should 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 physiological 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.

Donald B. Louria, M.D., is chairman emeritus of the Department of Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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