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Aging: The Reality

Demography of Human Supercentenarians

Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles.

Address correspondence to L. Stephen Coles, MD, PhD, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-7313. E-mail: scoles{at}ucla.edu

	Abstract

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An international committee of demographers has created a carefully documented list of worldwide living supercentenarians (110 years old) that has been published by the Los Angeles Gerontology Research Group on its web site and updated on a weekly basis for the past 6 years [see "snapshot" for the year 2003 in the Appendix]. What can be learned by studying this distinguished group of individuals? Also, what are the implications for understanding the fundamental biological limits to human longevity and maximum life span? Our conclusion: Although everyone agrees that average life expectancy has systematically advanced linearly over the last century, it is not realistic to expect that this pace can continue indefinitely. Our data suggest that, without the invention of some new unknown form of medical breakthrough, the Guinness Book of World Records benchmark established by French woman Jeanne Calment of 122 years, set back in 1997, will be exceedingly difficult to break in our lifetime.

According to the best evidence from paleontology, anthropology, molecular biology, and many other sources, the "longevity determination" for our own species occurred approximately 160,000 years ago when we climbed down from the trees and began to walk on the ground for long distances. As hominids, we distinguished ourselves from our primate cousins, and our species-specific maximum life span probably lengthened in comparison with chimps, apes, and monkeys, most likely due to the survival advantage of grandparenting and the value of having at least a few living elders within a tribe (2). Thus, the maximum human life span that could potentially be expressed by our human genome under ideal conditions (without predation or other trauma, but without such novel interventions such as genetic engineering) turned out to be 125 years (the oldest documented person we know of was 122 when she died in 1997). However, nothing like this age could ever have been witnessed until an unexpected event occurred during the course of the last 10,000–15,000 years—the establishment of what we now call "civilization." We were thus able to observe a brand new biological phenomenon called aging or "senescence"—something that had never been observed before in nature. Recall that there are no really old animals, except in zoos, and zoos by definition can only be sustained under very special conditions.

	WORLD CENTENARIANS

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It is acknowledged that the number of centenarians is increasing rapidly throughout the world. Analysis of data from Japan, for example, where female life expectancy at birth is approaching the assumed limit of 85 years, provides useful information on the rate at which these demographic changes is accelerating. Adjusted for the size of the birth cohorts, the Centenarian Doubling Time (CDT)—the number of years needed to double the total number of centenarians—halved in just 29 years. Moreover, death rates at 100 years and older show a clear decrease providing that males aged 105 years and older are excluded (3).

For the American population in 1990, the U.S. Census Report estimated that there were 37,306 persons older than age 100. However, the number 28,000 is likely to be more accurate, discounting an expectedly large number of false claims and unreported deaths. Ten years later, the 2001 Census counted 48,427 centenarians in the United States (out of a total of 281.4 million Americans). Again, for the year 2001, the number 42,000 is a better guess, after removing what is expected to be a large number of false claims and unreported deaths. By 2050, the Census Bureau estimates that the number of American centenarians will grow to 834,000 and double every 10 years thereafter (R. Young, Personal Communication, Atlanta, Georgia [ryoung{at}grg.org]). A graphical projection of the United States centenarian population shows an exponential rise starting with the year 2000 and extending through the end of the next century.

	WORLDWIDE SUPERCENTENARIANS

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The Gerontology Research Group (GRG), affiliated with the UCLA School of Medicine, has compiled and maintained tables of worldwide supercentenarians for the last 6 years (for example, see the Appendix for the 2003 table of supercentenarians). An international committee of approximately 30 demographers located in various countries throughout the world has worked diligently over at least the last 5 years to identify such persons in their local countries and rigorously translate their native language documentation into English to help validate individual claims. This committee principally communicates by e-mail and fax with all its members on a monthly basis. The numbers of such longevous persons has remained relatively stable, ranging from 36–46 individuals per annum over the past several years. The current version of this table is updated on a weekly basis and can be found on the Internet at http://www.grg.org/calment.html. This web site page also contains over 100 photographs of the oldest known men and women; also, there are more-detailed demographic tables [A–G] that contain lists of past-documented supercentenarians as recorded throughout history.

At the end of 2003, the international committee documented 45 living supercentenarians. The gender ratio (GR) was approximately 90% women (41 women to 4 men). But the GR and the distribution of nationalities were subject to significant fluctuations over time. Similarly, the absolute number of individuals in this table goes up and down, as newly entering members live long enough while other members pass on. A simple line graph of the numbers of supercentenarians over the last 5 years tends to oscillate like a noisy "stock market ticker tape," with a somewhat moderate upward tendency. Even though it would be a simple matter to plot a straight-line linear regression with a modestly positive slope through the points, to extrapolate this line far into the future would be risky, considering the fact that these points are embedded in so much noise. In other words, one cannot really say with authority that the maximum life span records of our species will ever be broken systematically in the coming decades like athletic records have been seen to fall regularly. Recall that the oldest known Guinness Book of World Records case is that of French woman Jeanne Louise Calment, who died on August 4, 1997 at the age of 122 years, 164 days.

A significant omission from our database is an assessment of potential supercentenarians from two of the largest Asian countries: India and China. As soon as we identify native-speaking demographers to help us in these countries (as well as other countries in Southeast Asia such as South and North Korea, Thailand, Viet Nam, and Indonesia), we are sure to expand our table somewhat, and we would be pleased to recruit volunteers from these regions from among the readers of this article.

Note that, for the United States, the 2000 Census counted 1388 supercentenarians. However, the Social Security Administration (SSA) has registered only 140 supercentenarians on their rolls, and this is still assumed to be an excessive number, due to lack of manpower to validate such claims (4). Indeed, physicians employed by the SSA have sought the GRG's advice about how to validate their own list of claimants. Of the 140 claimed, at least one third (and maybe more) is assumed to be exaggerated. Thus, the true number of United States supercentenarians now living is estimated to be closer to 75. For comparison, at of the end of 2003, the GRG validated—using much more rigorous standards for birth documentation—only 20 living American supercentenarians (see Appendix and Acknowledgments below). The discrepancy between the 20 we know of and the estimate of 75 total has to do with our own limitations in identifying these individuals in the first place and our rigorous methodology for validation that is intended to exclude a vast number of false claims.

Background of Tables
The data needed to create the table in the Appendix was compiled by an international team of contributors, including professional demographers, university-based centenarian researchers, as well as a number of highly dedicated amateurs who have devoted countless hours over the last 6 years to the task of maintaining its accuracy. Along the way, many journalists from different parts of the world, who normally write human interest stories on local celebrities, have assisted us in our contacts with family members who in turn provide official documentation. Nursing home staff in various parts of the country have also been extremely helpful. Note that the contributors work diligently to meet the challenge of various pretenders-to-membership whose documentation is either forged or lost for a variety of reasons. Many such individuals have been carefully omitted. Furthermore, the table is certainly incomplete in that, for less-developed countries, many individuals, who may otherwise have valid claims, have incomplete documentation (such as a family Bible), and official documents may never have existed in these countries, if and when they began keeping census records at all. Besides, birth certificates, baptismal certificates, and marriage certificates are often used when available. Finally, we may not even become aware of many of these individuals, since their families, even if they were to become aware that such a list was being maintained, might have no incentive to inform us or any government officials simply because demographers happen to be gratuitously interested in their family members.

Privacy Statement
For reasons of confidentiality, details of the supporting documentation of these individuals who are filed with the GRG will only be made available to legitimate demographic researchers having a "need to know." An important feature of our research protocol is our focus on persons whose age has been rigorously validated. For a complete validation of the age of a supercentenarian, it is frequently necessary to obtain personal information. For example, in most countries the precise name of a person is needed to retrieve and match birth and death certificates. Appropriate procedures and rules are designed to protect the confidential nature of personal information, taking into account prevailing data and protection laws of many different countries. For example, Germany has different laws from France and the United Kingdom. Data protection procedures and rules informally adopted by our committee, as well as the International Data Base on Longevity (IDL), are governed by the general principle that private data about individual persons should not be accessible from information that will eventually be made public unless essential for identification purposes. For example, among these rules is the provision that only specially trained validation personnel shall have access to private personal information (such as addresses, phone numbers, names of relatives, and so forth). This sort of private personal information shall not be made available to individuals who are external to the validation process and will never be included in a public version of our database.

We believe that these tables may shed important light on the biological limits of human morbidity and mortality. In the future, we will attempt to summarize this data in the context of human life history tables over time, as well as similar tables derived from other mammalian species, to provide us with a realistic perspective on the problem of long-term interventions that can reasonably be achieved in our lifetime.

Common Supercentenarian Phenotypes
Based on 7 personal interviews with supercentenarians (45-minute videotape with custom medical history) in the greater Los Angeles area, we have observed a number of characteristics that these individuals appear to share. We recognize that 7 individuals is a very small series of cases, and these data are very preliminary. We wish to alert the reader to the need to build a much larger series with well-defined and reproducible/validated measures.

• Significantly hard-of-hearing (usually bilaterally, but one ear may be favored; their deafness can sometimes be corrected by hearing aids).
  
• Significant blindness (despite eyeglasses and/or cataract surgery; macular degeneration is not correctable).
  
• Reduced sensorium for other senses, such as smell and taste, although no empirical evidence was taken.
  
• Poor dentition (usually, but not always, corrected by full dentures).
  
• Significant frailty (sarcopenia) (muscle weakness caused all of the participants to be confined to bed or to a wheelchair).
  
• Thin skin (stiff, leathery, easily injured, and hard to heal).
  
• Poor orientation (x3 = person, place, and time) (significant neurodegenerative disease, senility, or other dementia in at least 1 of the cases, but all 7 possessed fair long-term memory), untrained examiners frequently mistake deafness for dementia, since the participants can often answer questions correctly providing that the examiner waits patiently; however, they will often generate answers, simply to please the questioner (for example, "To what do you owe your exceptional longevity?" results in a variety of mutually inconsistent claims).
  
• Early health status was excellent (most virtually never needed to see a doctor before the age of 90); this tells us immediately that our modern medical establishment cannot claim credit for those who exhibit extreme longevity. These extreme ages are achieved in spite of what we would call poor lifestyle choices (such as heavy smoking, heavy drinking, or both, failure to exercise on a regular basis, and no conscious effort to eat nutritiously). None of our participants, however, were obese.
  
• Nearly all of our cases have long-lived siblings (aged 85 years and older) and most have a sibling (and many times several such siblings) who reached 95 or older. Citing a few cases from the Appendix, Charlotte Benkner's sister, Tillie, died last month at age 99. Her mother lived to age 99, and her father to age 92. Joan Riudavets-Moll, 114, has a 103-year-old brother and a 96-year-old brother. Grace Thaxton's mother lived to 109. Sophia DeMuth, who reached 111, has a daughter who is older than 105 at last count. A careful analysis of these statistics has yet to be done, but these anecdotal cases suggest that genes are extremely important and longevity tends to run in families.
  
• Postmortem autopsy (necropsy) data is not readily available, generally due to the wishes of the family members. However, it would be extremely valuable to learn whether the cellularity within adult supercentenarian tissues was significantly reduced on an organ-by-organ basis (replaced by fibrosis) as we suspect or whether cell numbers were within reasonable limits but cell volumes were significantly reduced.
  

Demography of Supercentenarians
In the year 2000, the U.S. Census Bureau reported only 1400 supercentenarians compared with 2700 in 1990 (about one half of the discrepancies were eliminated by simply comparing the dates of birth with the claimed ages, which were often the result of subtraction errors). In 2002, the SSA admitted that there were actually 139 persons aged 110 or older receiving Social Security benefits. Because most of these cases are exaggerated, the true number is more likely to be between 75 and 100 persons. Nevertheless, we cannot draw any conclusions at this time about whether these numbers over the last 10 years are actually growing (even thought they may seem to be).

Moreover, the total number of living supercentenarians cited above has frequently been misconstrued in the news media as representing every single person in the world aged 110 and over. The actual estimated number of worldwide living supercentenarians is more likely to lie between 300–450 persons, while for the United States, we estimate something like 75–100 as stated above.

While the total number of validated cases cited earlier is seen to be only approximately 10% of the suspected real-world total, it should also be noted that the bulk of the true supercentenarians actually falls between 110–113 years; hardly any survive to live past 115. Our estimate of 300–450 persons is based on a survival percentage of centenarians-to-age-110 between 0.15%–0.25% (4).

But why are we so cautious in accepting seemingly well-intentioned relatives' claims at face value? It should be appreciated that a majority of those claiming to be aged 110 years or older worldwide have subsequently been proven to be false. These individuals and more often their family, friends, and their business associates have their own personal motives for claiming these people as supercentenarians and, we are sad to report, are disingenuous, often intended to gain publicity for the tourist industry in their particular country. Occasionally, "age creep" occurs, in which individuals disproportionately gain years without any specific intent to deceive.

Are Numbers of Supercentenarians Increasing on a Per Capita Basis?
We believe that the increasing number of cases that we have observed during the last 40 years are the result of at least two factors:

1. Better methods for identifying and documenting these individuals, not to mention the diligence of our own committee members throughout the world who deserve all of the credit; and
   
2. Far more persons are reaching age 110 than ever before. That is, people who were dying at 105–109 years are now reaching 110–113 years of age, and the population is much, much larger, allowing more very rare events to appear.
   

Please note that the SSA data show that both of these reasons are major factors, and that it would be incorrect to ascribe all of the increase either due to an actual increase in longevity or due to better record keeping.

Therefore, there is no statistical evidence to support the hypothesis that the absolute number of known supercentenarians is increasing as a simple percentage of the total human population, although there is some evidence from animal studies that a reduction in the force of evolution after age 90 changes population mortality from an exponentially increasing rate to a constant rate in the oldest-old (5). This has become an important area of research in biodemography, and all the answers are not in yet (6).

In the life history of a species, reproductive competence begins, by definition, at 100% starting at puberty and then moves gradually toward 0% at the age of menopause for females (or andropause for males). The typical mortality rate for a species may then show a change in its normal exponential pattern. For convenience, demographers plot mortality as a positive slope straight-line logarithmic function (an exponential function of time). Around the time of menopause, there may be a change from a line with positive slope to one of zero slope (which represents a linear mortality function over time). This creates what is seen as a "knee" or "plateau" in the upward log-mortality regression line, which is empirically observed for many species. For humans, this knee is empirically observed to occur around age 95 (presumably the normal age of menopause is subject to a "grandparenting" effect that occurs for us but only rarely in other mammals). In other words, if a human being manages to make it to the age of 95, the exponential force of mortality may actually ease off a little, allowing a human centenarian to live a bit longer than they otherwise might if the forces of mortality were to have continued as an exponential function postmenopause/postandropause.

	INTERVENTIONS SUGGESTED BY SUPERCENTENARIAN DATA

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Throughout the ages, many foolish suggestions have been put forth for how to solve "the problem of aging." For example, in the 13th century, British mathematician and scientist Sir Roger Bacon, who was far ahead of his time in believing the world was spherical rather than flat, nevertheless claimed that "inhaling the breath of young virgins would rejuvenate very old men"(7). In recent years, a more informed understanding of the biochemical and neuroendocrine determinants of aging has put modern interventions on a somewhat more sound scientific foundation. Theoretical studies in the new field of Systems Biology are now under way to elucidate the regulatory mechanisms of the aging process at both cellular and molecular levels. We expect that practical applications of these studies will translate into genuine clinical and therapeutic interventions in the coming decades.

For example, a recently formulated two-step proposal to achieve rejuvenation using a stem cell command language could stimulate a recapitulation of organogenesis in situ, while still preserving overall adult tissue architecture. This process, sometimes called neoteny, has been observed to occur in nature in a few species (lizards and hive insects such as ants, bees, and termites).

Step 1: By means of protein and gene expression microarrays, identify and characterize the chemokines used during mammalian embryogenesis that could stimulate (or inhibit) adult stem cells to undergo mitotic division in the context of adult tissues without provoking multiple teratoma formation or other forms of cancer.

Step 2: Formulate a drug discovery program around these newly identified proteins to find out which ones did what. This would first need to be accomplished in vitro (tissue culture) and later in vivo, first with a rodent model and later followed by human clinical trials.

To facilitate future work in this field, we recommend the establishment of a National Supercentenarian Research Agenda: 1) create an epidemiological/demographic database that could be used to forecast population trends in aging; 2) understand the fundamental basis of age-associated degenerative conditions and nonfatal chronic illness; and 3) set a priority for documenting and implementing effective programs in prevention that could improve our health and thereby mitigate the economic consequences of unnecessary morbidity among our geriatric patients. Demographers have forecast that there are going to be a great many more older adults in the next few decades, and it will be important for all of us as we approach our senior years to be in good health with the expectation that we will soon benefit from the medical science that is now under way in research laboratories around the world.

	CONCLUSION

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A well-recognized demographer, Dr. James Vaupel, Director of the Laboratory of Survival and Longevity at the Max Planck Institute for Demographic Research in Rostock, Germany, has stated, "There is no fixed life span. There is no wall of death dictated by basic biology that we are edging toward. People are living longer and longer, and there is no reason to think the trend will slow or stop in the foreseeable future" (8). He cites some statistics that we agree with: "From 1840 until today, the life expectancy in the countries that are doing the best has increased two-and-a-half years per decade. It's linear, absolutely linear, with no evidence of any decline or tapering off. Why can't it continue to go up?" He continues, "If there were a fixed limit to human lifespans and we were approaching it, then the countries whose populations live the longest should be having more and more trouble making progress. But that's not true at all." He says, "For the past 20 years, Japan has been the leader, and every year the Japanese life expectancy goes up by a quarter of a year. There is no evidence that it is slowing. Japanese women," he adds, "now have a life expectancy of 85.23 years. And do we notice that death rates at age 80, 90, 100 are bottoming out? No, they're not," Dr. Vaupel says. "Death rates at those ages are coming down faster and faster. The death rates at age 80 are coming down about 2 percent a year in most countries." Then, a journalist asks, "But there has to be a limit, right?" "Why?" Dr. Vaupel replies. "While small but consistent increases in the average life span are not going to lead to immortality," he says, "there is no reason to assume that we know where progress will stop. There is no reason that life expectancy can't continue to go up two to three years per decade," Dr. Vaupel said. "Biomedical progress is really very impressive. We are beginning to understand cancer, heart disease, Alzheimer's Disease. In animal models, we are beginning to understand how to slow aging itself." Dr. Vaupel predicts that by midcentury, some countries may have life expectancies approaching 100 and says other researchers who share his views predict that life expectancies might approach 130 by 2050. "I'm not an optimist," Dr. Vaupel said. "I'm middle of the road." See de Grey (9) and Richel (10) for a more detailed discussion by those who are on the other side of Vaupel that put him in the middle of the road, so to speak.

As with Dr. Vaupel, we have also observed that widespread interventions by doctors and engineers using sophisticated public health measures, such as sewage treatment plants for fresh water, vaccines and antibiotics to prevent fatal epidemics, and much better obstetric techniques for delivering premature babies or saving mothers' lives in childbirth have significantly "rectangularized" historical human longevity curves over the last century. We are delighted to note that this process or rectangularization is continuing unabated. In other words, we are indeed witnessing an increase in average life expectancy throughout the industrialized world at a linear pace (albeit at a somewhat slower rate).

Nevertheless, after tracking the data in our supercentenarian tables over the last 5 years, there is no evidence demonstrating a corresponding "right-shift" in the maximum life span for our species. What if, in the process of eliminating premature death secondary to the acute conditions that we have successfully dealt with in the last century, we expose truly fundamental biological limitations on life expectation dictated by the human genome itself? Then, the optimism expressed above by Dr. Vaupel and others about "no limits to human lifespan" would be completely unwarranted.

We have had an opportunity in this discussion to address specifically the question of whether large extensions of human life expectancy are possible, and they may well be if they are based on interventions that have not yet been described in the scientific literature (but this may also be indulging in wishful thinking). Given what we have observed about extremely elderly people, we do not foresee any intervention-based standard medical practice (dietary, exercise, pharmacologic therapeutics, surgery, and so forth) either now or in the next 5 to 10 years that will make even the slightest bit of difference in the absolute numbers of supercentenarians that we can expect to identify. As we stated above, many of our subjects had not seen a doctor until they were 90. However, we do expect that their numbers will increase somewhat for statistical reasons (i.e., the larger cohorts that are expected to enter this category).

So, is there anything on the horizon that would permit supercentenarians to live an additional 40 years or more and thereby break outstanding human longevity records? Under present circumstances, our own data suggest that this will not happen. However, our evidence is anecdotal and certainly not conclusive. Among the nursing home patients we have interviewed, the quality of life of several of the centenarians we have encountered has remained remarkably high throughout their entire lives. Several centenarians we interviewed, for example, lived independently (without live-in support); one still possessed his California driver's license, had an active social life, and participated in senior sports. Several had such busy calendars that they had to rush to meet appointments following their interviews. However, even though these individuals exist, they are exceptionally rare. On the other hand, without exception, the quality of life of the supercentenarians we have identified and the smaller number we have studied in detail, given their severe frailty (sarcopenia), sharply reduced sensorium (significant degrees of blindness and deafness), and some degree of dementia, suggests that it is not realistic to expect that future supercentenarians will live much longer than the present cohort of the population that is already our longest lived. Therefore, to summarize—without the development of some new form of medical breakthrough—we believe that the barrier to exceeding the Guinness Book of World Records mark of 122 years set in 1977 by French woman Madame Jeanne Calment will be exceptionally difficult to achieve in our lifetime, even as we continue to celebrate her extraordinary contribution to our demographic investigations (11–47).

	Acknowledgments

	Footnotes

 
Decision Editor: James R. Smith, PhD

Received January 31, 2004

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