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The Longevity Dividend

FEATUREThe Longevity Dividend Redrawn from Koloman Moser's Frommes KalendarIllustrations by Joelle Bolt an intervention, such as a pill, that could significantly reduce your risk of cancer. Imagine an intervention that could reduce your risk of stroke, or dementia, or arthritis. Now, imagine an intervention that does all these things, and at the same time reduces your risk of everything else undesirable about growing older: inc

By | March 1, 2006

FEATURE
The Longevity Dividend
In Pursuit of the Longevity Dividend: What should we be doing to prepare for the unprecedented aging of humanity? By S. Jay Olshansky, Daniel Perry, Richard A. Miller, Robert N. Butler
Imagine...
Redrawn from Koloman Moser's Frommes Kalendar
Illustrations by Joelle Bolt

an intervention, such as a pill, that could significantly reduce your risk of cancer. Imagine an intervention that could reduce your risk of stroke, or dementia, or arthritis. Now, imagine an intervention that does all these things, and at the same time reduces your risk of everything else undesirable about growing older: including heart disease, diabetes, Alzheimer and Parkinson disease, hip fractures, osteoporosis, sensory impairments, and sexual dysfunction. Such a pill may sound like fantasy, but aging interventions already do this in animal models. And many scientists believe that such an intervention is a realistically achievable goal for people. People already place a high value on both quality and length of life, which is why children are immunized against infectious diseases. In the same spirit, we suggest that a concerted effort to slow aging begin immediately - because it will save and extend lives, improve health, and create wealth.

The experience of aging is about to change. Humans are approaching old age in unprecedented numbers, and this generation and all that follow have the potential to live longer, healthier lives than any in history. These changing demographics also carry the prospect of overwhelming increases in age-related disease, frailty, disability, and all the associated costs and social burdens. The choices we make now will have a profound influence on the health and the wealth of current and future generations.

GERONTOLOGY COMES OF AGE

Gerontology has grown beyond its historical and traditional image of disease management and palliative care for the old, to the scientific study of aging processes in humans and in other species-the latter is known as biogerontology. In recent decades biogerontologists have gained significant insight into the causes of aging. They've revolutionized our understanding of the biology of life and death. They've dispelled long-held misconceptions about aging and its effects, and offered for the first time a real scientific foundation for the feasibility of extending and improving life.

The idea that age-related illnesses are independently influenced by genes and/or behavioral risk factors has been dispelled by evidence that genetic and dietary interventions can retard nearly all late-life diseases in parallel. Several lines of evidence in models ranging from simple eukaryotes to mammals suggest that our own bodies may well have "switches" that influence how quickly we age. These switches are not set in stone; they are potentially adjustable.

Biogerontologists have progressed far beyond merely describing cellular aging, cell death, free radicals, and telomere shortening, to actually manipulating molecular machinery and cell functions.1 These recent scientific breakthroughs have nothing in common with the claims of entrepreneurs selling alleged anti-aging interventions they say can slow, stop, or reverse human aging (see Your Money for Your Life for a peek at this industry). No such treatment yet exists.

Nevertheless, the belief that aging is an immutable process, programmed by evolution, is now known to be wrong. In recent decades, our knowledge of how, why, and when aging processes take place has progressed so much that many scientists now believe that this line of research, if sufficently promoted, could benefit people alive today.2,3 Indeed, the science of aging has the potential to do what no drug, surgical procedure, or behavior modification can do-extend our years of youthful vigor and simultaneously postpone all the costly, disabling, and lethal conditions expressed at later ages.

In addition to the obvious health benefits, enormous economic benefits would accrue from the extension of healthy life. By extending the time in the lifespan when higher levels of physical and mental capacity are expressed, people would remain in the labor force longer, personal income and savings would increase, age-entitlement programs would face less pressure from shifting demographics, and there is reason to believe that national economies would flourish. The science of aging has the potential to produce what we refer to as a "Longevity Dividend" in the form of social, economic, and health bonuses both for individuals and entire populations-a dividend that would begin with generations currently alive and continue for all that follow.

We contend that conditions are ripe today for the aggressive pursuit of the Longevity Dividend by seeking the technical means to intervene in the biological processes of aging in our species, and by ensuring that the resulting interventions become widely available.

WHY ACT NOW?

Consider what is likely to happen if we don't. Take, for instance, the impact of just one age-related disorder, Alzheimer disease (AD). For no other reason than the inevitable shifting demographics, the number of Americans stricken with AD will rise from 4 million today to as many as 16 million by midcentury.4 This means that more people in the United States will have AD by 2050 than the entire current population of the Netherlands. Globally, AD prevalence is expected to rise to 45 million by 2050, with three of every four patients with AD living in a developing nation.5 The US economic toll is currently $80-$100 billion, but by 2050 more than $1 trillion will be spent annually on AD and related dementias. The impact of this single disease will be catastrophic, and this is just one example.

Cardiovascular disease, diabetes, cancer, and other age-related problems account for billions of dollars siphoned away for "sick care." Imagine the problems in many developing nations where there is little or no formal training in geriatric health care. For instance, in China and India the elderly will outnumber the total current US population by midcentury. The demographic wave is a global phenomenon that appears to be leading health care financing into an abyss.

Nations may be tempted to continue attacking diseases and disabilities of old age separately, as if they were unrelated to one another. This is the way most medicine is practiced and medical research is conducted today. The National Institutes of Health in the United States are organized under the premise that specific diseases and disorders be attacked individually. More than half of the National Institute on Aging budget in the United States is devoted to AD. But the underlying biological changes that predispose everyone to fatal and disabling diseases and disorders are caused by the processes of aging.6 It therefore stands to reason that an intervention that delays aging should become one of our highest priorities.

HEALTH AND LONGEVITY CREATE WEALTH

According to studies undertaken at the International Longevity Center and at universities around the world, the extension of healthy life creates wealth for individuals and the nations in which they live.7 Healthy older individuals accumulate more savings and investments than those beset by illness. They tend to remain productively engaged in society. They spark economic booms in so-called mature markets, including financial services, travel, hospitality, and intergenerational transfers to younger generations. Improved health status also leads to less absenteeism from school and work and is associated with better education and higher income.

A successful intervention that delays aging would do more than yield a one-time benefit, after which, one might argue, the same exorbitant health-care expenses would ensue. Life extension already achieved among animals suggests that delayed aging may produce a genuine compression of mortality and morbidity.8 Calorie-restricted animals not only experience a reduction in their risk of death, but also experience declines in the risk of a wide variety of age-sensitive, nonlethal conditions such as cataracts, kidney diseases, arthritis, cognitive decline, collagen cross linking, immune senescence, and many others.9 If this could be achieved in people, the benefits to health and vitality would begin immediately and continue throughout the remainder of the lifespan. Thus the costly period of frailty and disability would be experienced during a shorter duration of time before death. This compression of mortality and morbidity would create financial gains not only because aging populations will have more years to contribute, but also because there will be more years during which age-entitlement and healthcare programs are not used.

A MATURING SCIENCE

Centuries ago, the French naturalist Buffon observed that aging exhibits common characteristics across species. Recent work in genetics and in the comparative biology of aging confirms these impressions and provides important clues about how to develop effective interventions that delay aging. It is now clear that some of the hormones and cellular pathways that influence the rate of aging in lower organisms also contribute to many of the manifestations of aging that we see in humans, such as cancers, cataracts, heart disease, arthritis, and cognitive decline. These manifestations occur in much the same way in other animals and for the same biological reasons.10 (For more on one example see Aging research for the dogs, below). Several experiments have demonstrated that by manipulating certain genes, altering reproduction, reducing caloric intake, and changing the signaling pathways of specific physiological mechanisms, the duration of life of both invertebrates and mammals can be extended.11,12 Some of the genes involved, such as PIT1, PROP1, and GHR/BP, modulate the levels of hormones that affect growth and maturation; others, such as p66SHC, help individual cells avoid injury and death. No one is suggesting that alteration of these genes in humans would be practical, useful, or ethical, but it does seem likely that further investigation may yield important clues about intervening pharmacologically.

Genes that slow growth in early life - such as those that produce differences between large, middle-size, and miniature dogs - typically postpone all the signs and symptoms of aging in parallel. A similar set of hormonal signals, related in sequence and action to human insulin, insulin-like growth factor (IGF-I), or both, are involved in aging, life span, and protection against injury in worms, flies, and mice, and extend life span in all of those animals. These hormones help individual cells buffer the toxic effects of free radicals, radiation damage, environmental toxins, and protein aggregates that contribute to various late-life malfunctions.

An extension of disease-free lifespan of approximately 40% has already been achieved repeatedly in experiments with mice and rats.13-16 These examples provide powerful new systems to study how aging processes influence disease expression and will yield clues about where to look for interventions that can slow aging in people in a safe and effective way. Since many of the biological pathways of aging are conserved also in simple invertebrate species such as fruit flies, it should be possible to experimentally evaluate candidate intervention strategies rapidly.

Some people, including a proportion of centenarians, live most of their lives free from frailty and disability. Genetics plays a critical role in their healthy survival. Identifying variation in these subgroups of humans holds great potential for improving public health. For example, microsomal transfer protein (MTP) on chromosome 4 has been identified as a longevity modifier in a sample of centenarians17; there is strong evidence linking a common variant of KLOTHO, the KL-VS allele, to human longevity18; and it has been demonstrated that lipoprotein particle sizes promote a healthy aging phenotype through codon 405 valine variation in the cholesteryl ester transfer protein (CETP) gene.19

Given the speed at which the study of aging has advanced and the ability to obtain research results quickly from the study of short-lived species, scientists have reason to be confident that a Longevity Dividend is a plausible outcome of aging research.

THE TARGET

What we have in mind is not the unrealistic pursuit of dramatic increases in life expectancy, let alone the kind of biological immortality best left to science fiction novels.20 Rather, we envision a goal that is realistically achievable: a modest deceleration in the rate of aging sufficient to delay all aging-related diseases and disorders by about seven years.21 This target was chosen because the risk of death and most other negative attributes of aging tends to rise exponentially throughout the adult lifespan with a doubling time of approximately seven years.22 Such a delay would yield health and longevity benefits greater than what would be achieved with the elimination of cancer or heart disease.23 And we believe it can be achieved for generations now alive.

If we succeed in slowing aging by seven years, the age-specific risk of death, frailty, and disability will be reduced by approximately half at every age. People who reach the age of 50 in the future would have the health profile and disease risk of today's 43-year-old; those aged 60 would resemble current 53-year-olds, and so on. Equally important, once achieved, this seven-year delay would yield equal health and longevity benefits for all subsequent generations, much the same way children born in most nations today benefit from the discovery and development of immunizations.

A growing chorus of scientists agrees that this objective is scientifically and technologically feasible.24 How quickly we see success depends in part on the priority and support devoted to the effort. Certainly such a great goal - to win back, on average, seven years of healthy life - requires and deserves significant resources in time, talent, and treasury. But with the mammoth investment already committed in caring for the sick as they age, and the pursuit of ever-more expensive treatments and surgical procedures for existing fatal and disabling diseases, the pursuit of the Longevity Dividend would be modest by comparison. In fact, because a healthier, longer-lived population will add significant wealth to the economy, an investment in the Longevity Dividend would likely pay for itself.

THE RECOMMENDATION

The NIH is funded at $28 billion in 2006, but less than 0.1% of that amount goes to understanding the biology of aging and how it predisposes us to a suite of costly diseases and disorders expressed at later ages. We are calling on Congress to invest $3 billion annually to this effort, or about 1% of the current Medicare budget of $309 billion, and to provide the organizational and intellectual infrastructure and other related resources to make this work.

Specifically, we recommend that one-third of this budget ($1 billion) be devoted to the basic biology of aging with a focus on genomics and regenerative medicine as they relate to longevity science. Another third should be devoted to age-related diseases as part of a coordinated trans-NIH effort. One sixth ($500 million) should be devoted to clinical trials with proportionate representation of older persons (aged 65+) that include head-to-head studies of drugs or interventions including lifestyle comparisons, cost-effectiveness studies, and the development of a national system for postmarketing surveillance.

The remaining $500 million should go to a national preventive medicine research initiative that would include studies of safety and health in the home and workplace and address issues of physical inactivity and obesity as well as genetic and other early-life pathological influences. This last category would include studies of the social and economic means to effect positive changes in health behaviors in the face of current health crises - obesity and diabetes - that can lower life expectancy. Elements of the budget could be phased in over time, and it would be appropriate to use funds within each category for research training and the development of appropriate infrastructure. We also strongly encourage the development of an international consortium devoted to this task, as all nations would benefit from securing the Longevity Dividend.

With this effort, we believe it will be possible to intervene in aging among the baby boom cohorts, and all generations after them would enjoy the health and economic benefits of delayed aging. Such a monetary commitment would be small when compared to that spent each year on Medicare alone, but it would pay dividends an order of magnitude greater than the investment. And it would do so for current and future generations.

In our view, the scientific evidence strongly supports the idea that the time has arrived to invest in the future of humanity by encouraging the commensurate political will, public support, and resources required to slow aging, and to do so now so that most people currently alive might benefit from the investment. A successful effort to extend healthy life by slowing aging may very well be one of the most important gifts that our generation can give.

S. Jay Olshansky is professor of epidemiology and biostatistics at the University of Illinois, Chicago; Daniel Perry is executive director for the Alliance for Aging Research in Washington, DC; Richard A. Miller is professor of pathology at University of Michigan, Ann Arbor; and Robert N. Butler is president and CEO of the International Longevity Center in New York.

References
1. H. Warner, "Twenty years of progress in biogerontology," National Institute on Aging, 2005.
2. R.M. Miller, "Extending life: Scientific prospects and political obstacles," Milbank Q, 80:155-74, 2002.
3. Public Agenda, "The science of aging gracefully: Scientists and the public talk about aging research," The Alliance for Aging Research and the American Federation for Aging Research, 2005.
4. E. Liesi et al., "Alzheimer disease in the US population: Prevalence estimates using the 2000 census," Arch Neurol, 60:1119-22, 2003.
5. Alzheimer's Disease Annual Report, Alzheimer's Disease International, 2004-2005; www.frost.com/prod/servlet/dsd-fact-file.pag?docid=38565311
6. R.N. Butler et al., "The aging factor in health and disease: The promise of basic research on aging," Special Report, Aging Clin Exp Res, 16:104-12, 2004.
7. D. Bloom, D. Canning, "The health and wealth of nations," Science, 287:1207-9, 2000.
8. M. Vergara et al., "Hormone-treated Snell dwarf mice regain fertility but remain long-lived and disease resistant," J Gerontol A Biol Sci Med Sci, 59:1244-50, 2004.
9. R.A. Miller, S.N. Austad, "Growth and aging: Why do big dogs die young?" in Handbook of the Biology of Aging, E.J. Masoro, S.N. Austad, eds., New York: Academic Press, 2006, pp. 512-33.
10. D. Sinclair, L. Guarente, "Unlocking the secrets of longevity genes," Sci Am, March 2006, [in press].
11. M. Tatar et al., "The endocrine regulation of aging by insulin-like signals," Science, 299:1346-51, 2003.
12. R. Weindruch, R.S. Sohal, "Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging," New Engl J Med, 337:986-94, 1997.
13. H.M. Brown-Borg et al., "Dwarf mice and the ageing process," Nature, 384:33, 1996.
14. K. Flurkey et al., "Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production," Proc Natl Acad Sci, 98:6736-41, 2001.
15. B.P. Yu et al., "Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics," J Gerontol, 40:657-70, 1985.
16. R. Weindruch, R.L. Walford, The Retardation of Aging and Disease by Dietary Restriction, Springfield, Ill., Charles C. Thomas, 1988.
17. B.J. Geesaman et al., "Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan," Proc Natl Acad Sci, 100:14115-20, 2003.
18. D.E. Arking et al., "Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity," Circ Res, 96:412, 2005.
19. N. Barzilai et al., "Unique lipoprotein phenotype and genotype associated with exceptional longevity," JAMA, 290:2030-40, 2003.
20. H. Warner et al., "Science fact and the SENS agenda," EMBO Reports, 6:1006-8, 2005.
21. S.J. Olshansky, "Can we justify efforts to slow the rate of aging in humans?" Presentation before the annual meeting of the Gerontological Society of America, 2003.
22. R.N. Butler, J.A. Brody, eds., Delaying the Onset of Late-life Dysfunction, New York: Springer Publishing, 1995.
23. S.J. Olshansky, "Simultaneous/multiple cause delay: An epidemiological approach to projecting mortality," J Gerontol, 42:358-65, 1987.
24. S.J. Olshansky et al., "Position statement on human aging," J Gerontol Biol Sci, 57A: B1-B6, 2002.
An Aging Drug in Our Midst?

Recent results indicate that an approved diabetes drug, metformin, may battle aging. Approved in 1995, metformin was marketed as Glucophage. Now it and generic versions are the most widely used oral medication for type II diabetes. "There is a huge natural experiment with people on metformin," says Don Ingram, of the US National Institute on Aging. And, some data are beginning to look promising.

Animal studies with metformin show increased age and reduced tumor load, and although no clinical studies are looking directly at effects on aging, a variety of ongoing clinical trials in humans are investigating type II diabetes, metabolic syndrome, liver disease, and polycystic ovary syndrome. The UK Prospective Diabetes Study 34 showed that in patients with type II diabetes, metformin treatment resulted in reductions in end-organ damage, myocardial infarction, and all-cause mortality. Stephen Spindler, professor of biochemistry at the University of California, San Diego, has shown that metformin out-performs short-term calorie restriction in inducing the gene-expression changes associated with long-term calorie restriction.

Not everyone is persuaded by the metformin results, however. Side effects, such as a small risk of lactic acidosis that can be fatal in certain patients, are not likely worth the risk of lifelong treatment for aging. Nir Barzilai at the Albert Einstein College of Medicine in New York says, "Meformin is a terrific drug used in a large prospective study to prevent diabetes, but this does not mean it has any effects on aging beyond its specific role in preventing one of the age-related diseases."

-Michael O'Neill
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Comments

Avatar of: Ellen Hunt

Ellen Hunt

Posts: 199

December 29, 2008

By slowing aging, we should not expect to lower the number of years of debility, but to increase it. This is because lowering the rate of aging, will shift onset forward - but it will also slow the rate of onset of debility, which will extend that period of time in people's lives. (Assuming that aging is related to debility, controlled by the same systems.) This is basic mathematics. \n\nSo we will increase the load on our medical system, raising costs. \n\nAnother false assumption is that by increasing lifespan by 7 years we will have greater productivity. That is only true if we all decide to work until we drop dead, and never retire. That is probably what will wind up happening, given the economy, in one way or another. Increasing life span by 7 years will only make the huge economic problem we are now facing worse because fundamentally, the developed world's economic malaise is demographics driven. Entirely apart from corruption and war spending, the problem is that 2008 was the transition year when net inflows into markets for retirement were scheduled to be roughly balanced by net outflows because of the baby boomers. From this point forward, until the boomers die off and stop being economic liabilities, the developed world's economy will experience stagnation at best. Adding extra burdens of massive corruption, foolish spending on what does not return the investment will push us into depression. But this proposal will not improve matters as it stands. Anyone who thinks the retiring baby boomers are going to intentionally live longer in order to work until they die isn't living in the same world I am. \n\nAnother problem is that if we increase life span by delaying aging, will we also lower birth rate? Look around at the massive impact our species has on the biosphere right now. Doing this will improve matters how? Pushing this into the developing world might improve matters a bit by strengthening the cultural contribution of elders. But that is debatable. \n\nThere are many things to be worked out about enhancing life span, but this article isn't much of a contribution toward understanding them. It reads to me like a call for funding. Yes, I think we should fund anti-aging research. But we need to enunciate social goals very clearly to go along with it that are scientifically consonant with producing a better society. I'm sorry, but starry-eyed half-baked ideas about impact don't qualify.
Avatar of: anonymous poster

anonymous poster

Posts: 8

December 29, 2008

If/Since genes of an individual is hard to change, which is most important among the three factors listed header? probably both.\nWhat kind of drugs? probably customized one.\nWhat lifestyle? probably customized one as well.\nThere have been many longevity stars in the world, but their lifestyles are different. \nWhat are the most important factors in lifestyle for longevity: stress, nutrition, sleep, exercise, or others?\nWill life be longer without stress? If not and certain stress is needed, what degree/level of stress is appropriate for us to live longer?\n
Avatar of: Kevin Perrott

Kevin Perrott

Posts: 2

December 30, 2008

In response to Ms. Hunt in her comment entitled "Wait a moment here. Someone needs to check his math." I would like to make a few comments.\n\nFirstly, Ms. Hunt maintains that lowering the rate of aging will extend the years in disability. This statement actually goes against current evidence which shows the reverse to be true, that people are living longer and they are living BETTER, with a much longer time spent in relative good health with the length of disability about the same as it has always historically been and limited to the last year or so of life. \n\nIn terms of checking some more of the math, one could look to the latest report from the Milken Institute which describes an every increasing price tag of 1.3 trillion dollars per year to address age-related disease in the U.S. alone. We cannot truly calculate the level of human suffering this amount represents, but in hard economic terms there is no doubt that the sharp increase in the fragile elderly which will be experienced as the baby boomer generations reaches its 'golden years', will dramatically increase this amount and this is a pattern repeating itself in developed and developing nations all over the world. \n\nGlobal aging is 'elephant in the room' with the percentage of elderly populations set to reach 25% in many nations by 2030, however governments are ill-prepared to handle this looming problem because the problem is perceived as intractable. Instead programs to address global aging akin to rearranging the deck chairs on the Titanic seem an appropriate response to governments unaware of what else to do. \n\nWe are not however powerless in the face of combating the aging process anymore. New technologies such as stem cells and many new approaches in regenerative medicine stand poised to transform medical care for an increasingly frail population. As a society, we have a narrow window of opportunity to take advantage of these emerging technologies to blunt the silver tsunami threatening to envelope us all and with the savings in health care, we may just avoid bankruptcy at the same time we save hundreds of thousands of lives and increase the quality of life for millions and potentially billions of people.\n\nI am personally disturbed by Ms. Blunt's statement that "...until the boomers die off and stop being economic liabilities..." in that it indicates a truly stunning ability to put aside the fact that these drains on the economy are PEOPLE, and that compassion for the suffering of others is what drives us to develop methods to cure disease and comfort those so afflicted. This is however an all too common stance which people are able to make when they depersonalize the suffering of others, especially if they think nothing can be done about it. Additionally, by labeling an entire population as a 'liability', she completely discounts the value of the wisdom and experience that are acquired in life that, if housed in a healthy body, would serve as the most precious resource possible. A world with a large population of healthy and engaged elderly with perspectives borne of decades more life would be a substantially different place as the perennial problems of poverty, pollution and violence could be approached from a more mature position.\n\nFrom any standpoint, financial, ethical, or practical, there is no argument, social or otherwise, which can stand up to the fact that 100,000 mothers, fathers, sons, daughters, brothers and sisters, suffer and die everyday due to degenerative conditions which could potentially be addressed with emerging technologies. The consequences of the loss of these INDIVIDUALS are manifold and dwarf the potential negative consequences of adjusting the status quo to keeping them around. \n\nSuggesting that we should avoid developing technologies because of some imagined negative social consequence belies an ignorance of the very real and concrete urgent need for these technologies today. For those suffering, the questions are not academic and for their loved ones, there is little time to waste. Suggesting that we should forgo the opportunity to create such technologies when their creation becomes obvious and call people a "liability" is tantamount to failing to throw a line to a drowning man.\n\nThe way forward at least for me is clear; for the good of the economy and the good of the society we must take up the challenge of addressing global aging and fund longevity research. The payback of keeping people healthy and alive will be truly enormous to our economy and quality of life, just as it always has been for keeping anyone alive and able to engage productively with others.\n\n

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