X-Message-Number: 11852
From: "Thomas Nord" <>
Subject: Who Are Centenarians?| 
Date: Sun, 30 May 1999 03:43:36 +0100

Centenarians like Edith Blair Staton, age 102, have lived the history most
of us only read about. Mrs. Staton was acquainted with a number of American
presidents and met regularly with several First Ladies in her capacity as
national director of the Girl Scouts of America. She knew people who died
aboard the Titanic.

Written By Thomas T. Perls MD, MPH, FACP
Harvard Division on Aging, Beth Israel Deaconess Medical Center
Centenarians are the fastest growing segment of our population. The second
fastest is the age group 85+.
Currently, there are probably about 50,000 centenarians in the United
States, or a little more than 1 centenarian per 10,000 in the population
(the above estimate may be a relatively small over-estimation); 90% of them
are women, 10% are men. This prevalence rate is approximately the same, or a
little higher than other industrialized countries.
Why? Glossary
Age Validation: The process of verifying a person's age. In the case of
centenarians this may be by birth certificate, or multiple other forms of
proof that are consistent with one another. including the ages of family
members from various generations before and after the person in question.
Centenarian: Age 100 years or older.
Geriatrics: Pertaining to the medical care of older people.
Gerontology: The biomedical and social study of aging.
Life Expectancy (Average): The average number of years that an average
person of a given age maybe expected to live, usually as determined by
mortality tables.
Life Span: The age of death of the longest-lived member of the species.
Madame Calment has defined the life span of the human species as 122 years.
Neuropsychology: The branch of medicine pertaining to the study and
treatment of Neurological and psychological disorders.
Nonagenarian: A person age 90 years to 99 years old.
Octagenarian: A person age 80 years to 89 years old.
Prevalence: The number of cases of an observation in a specified population
at a given time.
Proband: The original individual, who because of their specific
characteristic (e.g. extreme longevity) causes a study of other family
members to determine if they have the same characteristic and if they have
hereditary or genetic factors in common that could explain such a
coincidence.
Relative Risk: The chance of an observation occurring in association with a
set of individuals compared to another set.
Super-Centenarian: Age 110 years or older.
The age composition of the population is changing dramatically. More and
more people are now able to achieve their individual life expectancy
potentials. This is a dramatic change from the turn of the century, when
many people died prematurely especially in infancy. In fact, at the turn of
the century, when our centenarians were young children, the population, in
terms of age, was in the shape of a steep triangle, with the vast proportion
being young and only a very few reaching very old age. At that time, 1 in
100,000 could expect to go on to be 100 years old. Now, the picture is very
different. We are experiencing a rectangularization of the population; more
and more people are living beyond the vulnerable childhood years and
achieving old age, so that the older group at the top ages nearly equals the
bottom.

A tremendous force in the population will drive the unprecedented growth of
the 65+ population in the early part of the next century -the baby boomers.
The first baby boomers recently turned 50 years old. Actually, this 70
million-strong group now constitutes the "elder boomer" generation! By the
first decade of the next century, there will be as many seniors as there are
people under the age of 20. Approximately 3 million of these elder boomers
can expect to become centenarians. An important component of the elder
boomers' disproportionate ability to achieve extreme age is their relatively
high level of education, income and attention to good health habits.

Are Centenarians a New Phenomenon?
Prior to the 20th century, average life expectancy was about 45 years of
age. However, one must distinguish between average life expectancy and life
span. Average life expectancy is the average age members of the population
survive to. Life span is the maximum age obtainable for the species and is
defined by the age of the oldest living individual. In the case of humans,
that individual was Madame Jeanne Calment who died at the age of 122 years
in August, 1997. Madame Calment therefore had a tremendous responsibility
... in her later years, every day she lived, she extended the human life
span by a day.

What Fountain of Youth?
Thomas Perls MD, MPH
(Letter to the Editor, NY Times, March 18, 1998)
To the Editor:
Re your March 14 front-page article on the scores of very old people living
in Lerik, Azerbaijan: Such a fountain of youth would be of incredible
scientific significance. However, don't you wonder why geneticists and
gerontologists aren't intensively studying this population?
The fact is, in the early 1980's American scientists did go to Azerbaijan
with high hopes and visions of discovering factors that slow down aging.
Instead, after careful investigation of the reported ages, they found them
to be off by a generation.
The centenarians were either using birth or church certificates of aunts or
uncles with the same names as their own or there just wasn't any reasonable
proof at all.
Cases of extreme longevity require detailed scrutiny because they would be
so incredibly rare. That is not to say that the elders of Azerbaijan are not
worth studying. The potentially high prevalence of people reaching at least
their 80s or even 90s in relatively good health despite third world
conditions is noteworthy.
THOMAS PERLS, M.D.
Cambridge, Mass., March 15, 1998
The writer is director of the New England Centenarian Study at Harvard
Medical School.

Prior to the twentieth century, though life expectancy was half of what it
is today, life span was probably not that different. There are numerous
instances of people living well into their nineties reported as far back as
the sixteenth century. Titian, the well known Italian master painter, lived
to at least age 90 and may have been as old as 99 years of age. Hippocrates
reportedly died in his mid eighties. To say that life span also doubled in
even the last thousand years would be hard to substantiate, especially from
an evolutionary point of view. For example, what genetic changes could
possibly occur over the course of a thousand years that would provide such
an enormous survival advantage?
There are several geographical areas which have claimed inhabitants with
extreme longevity, but after closer examination, these claims have been
found to be false. Vilacamba, Ecuador almost became a tourist attraction
because natives claimed their water was a fountain of youth leading to the
many super-centenarians in that region.
What about the reports of people in the Russian Caucases living to 150 years
and beyond? Remember the Dannon yogurt commercials? In fact, those purported
super-centenarians were taking on the identities of their parents, aunts and
uncles. Again, the oldest person from whom we have multiple forms of
proof-of-age is Madame Calment (see above).

Shirali Muslimov came to be known as "The Oldest Inhabitant of the Planet"
and allegedly lived to the ripe old age of 168.

These regions still merit careful study however. Though claims of extreme
age are untrue, there still may be an unusually high prevalence of very old
fit people in these regions. In the Tibetan mountains for instance,
octogenarian and nonagenarian elders, impressively many of them men, still
herd live stock and still lead physically strenuous lives.
For specific articles on age validation in these groups that disprove the
claims of extreme ages, see our Resources section.
Common Characteristics
We have been conducting a population-based study which attempts to find all
the centenarians within a given geographic area. As a result we are able to
determine prevalence of centenarians, prevalence of age-associated diseases
in centenarians, as well as their functional status, sociodemographic
characteristics and so on. The most important finding has been that all of
the subjects were independently functioning and in good health at least to
the age of ninety. This finding is consistent with two hypotheses: 1. One
has to be in excellent health in order to reach extreme old age and 2. These
subjects age slowly and either avoid or at least, markedly delay diseases
normally associated with aging (such as lethal cancers, Alzheimer's, stroke
and heart disease).
Geographic Clustering?
Though reports of people age 130 years and older are unfounded, there may be
truth to regions with unusually high prevalence rates. For example, in North
America, there may be a "centenarian belt" extending from Minnesota to Nova
Scotia. Preliminarily we have noted a prevalence rate of one centenarian per
5,000 in this population, which is about twice the rate in New England. Such
clustering could be due to a founder effect. That is, many of these
centenarians could come from ethnic backgrounds (e.g. Celtic, French) which
predispose them to extreme longevity. This hypothesis is based upon the
supposition that extreme old age does in fact run in families.
Familial Clustering
We have described two families with multiple centenarians within single
generations. Family "P" has three centenarian siblings and one nonagenarian
sibling and family "K" has four centenarian siblings and one nonagenarian
sibling. Such familial patterns of extreme longevity have not been described
before. We validated family member ages using the family reconstitution
method and by collecting corroborative evidence of age at multiple times in
the family members' lives.
We calculated the probability of the first family to be 1.5 families per
million families with the generation of note being born around 1880-1899.
Such odds could be consistent with "chance." The possibility of the second
family is much more improbable with siblings ages 108, 103, 102 and 101
years.
If such clustering of extremely old siblings does not occur by chance, but
rather it occurs because of common genetic and/or environmental factors,
then encountering such families would be much more probable than recently
believed.
If extreme old age does run in families, as suggested by these findings,
such families may be more common than previously thought. Further
delineation of other similar families and perhaps searching for discrete
genes and environmental factors that may be common among them may yield
important determinants of extreme longevity.
Older Mothers Live Longer (Reference 11, Below)
The most reliable predictor we have of when a woman will go through
menopause is the age at which her mother went through it. As of yet, we
don't know what genetic or environmental factors mothers and daughters have
in common to determine this association, but these same factors may also
influence rates of aging and susceptibility to diseases associated with
aging.
As we reviewed the pedigrees of a number of our centenarian subjects living
in the suburban Boston area, we came across a substantial number of women
who had children in their forties. There was even one that had a child at
the age of 53 years. This struck us as unusual given that maternal age
greater than forty is a relatively rare event. Less than 3 percent of births
occur in women 40 years of age or older. In 1995 the birth rate of American
women 40-44 years was 6.6 per 1000 women, and 0.3/1000 for women 45-49.
However, a history of older maternal age among our centenarian subjects made
sense to us since aging relatively slowly is a likely necessary
characteristic of achieving extreme age and women who do so, should be able
to bear children at an older age.

Women who naturally had a child in their forties are four times more likely
of living to a 100 years old rather than dying at the age of 73.

We went on to compare 78 female centenarians with a similar birth cohort of
fifty-four women born in 1896, but who died at of the age of 73 years in
1969. By collecting data on a similar birth cohort, we were able to minimize
concerns about temporally related influences upon fertility such as health
and contraception-related trends. We found that 19.2% of the centenarians
had children at age 40 years or older compared to 5.5% of the women who
lived to age 73.
We concluded that if you are a woman who naturally had a child in her
forties, you are four times more likely to live to 100 years old rather than
dying at the age of 73. However, we believe that it is not the act of having
a child in your forties that promotes long life, but rather that having a
child late in life is an indicator that the woman's reproductive system is
aging slowly. A slow rate of aging would therefore bode well for the woman's
subsequent ability to achieve very old age.
What are the factors that link the slowly aging reproductive system and the
ability to reach extreme age? Ideally, to identify the reproductive factors
which are associated with longevity we would like to know the status of
various reproductive factors such as age at menarche, cycle regularity,
number of spontaneous abortions and age of menopause. Unfortunately,
obtaining this type of information from relatives of the deceased is
difficult and unreliable. During the first quarter of this century,
fertility enhancing interventions for older women were not available. Under
these circumstances, knowing when a woman last had a child is our best
estimate of her premenopausal status and therefore reflects her natural
ability to have conceived later in life. Relatively delayed menopause, like
pregnancy after age 40, may be a marker for aging slowly and the subsequent
ability to achieve extreme longevity. This finding is interesting not only
for its potential value in predicting individuals predisposed to extreme
longevity, but also because it has implications regarding the theoretical
basis of menopause and human life span.
Siblings of Centenarians Live Longer (See Reference 15, Below)
While conducting a population-based study of centenarians, we were struck by
the large number of subjects who also had long-lived siblings. Comparing the
survival rates of siblings of centenarians and of the siblings of a similar
birth cohort who died in their early seventies, we found the siblings of our
centenarian subjects had a 4 times greater chance of surviving to their
early nineties.
Using town censuses, we located and recruited 102 centenarians (10 males, 92
females) and their families living in the Eastern Massachusetts area. The
control group was a similar birth cohort consisting of people born in 1896,
but who died at 73 years of age in 1969 (n=77, 28 males, 49 females). We
located the next-of-kin of these subjects using data provided by the
Massachusetts State Registry of Vital Records and subsequently death notices
appearing in the 1969 Boston Globe. Birth dates and current age or age at
death of siblings of both groups were obtained from next-of-kin. By
comparing subjects with similar years of birth, we controlled for
time-dependent influences on survival such as trends in health care, illness
outbreaks (e.g. the influenza epidemic of 1919), war (e.g. WWI), and
fluctuations in the economy (e.g. the boom of the 1920's and the Great
Depression). The centenarians had a total of 456 siblings (233 males, 223
females) and the 73-year-olds had a total of 240 siblings (121 males, 119
females). The two groups of siblings were not statistically different in
birth place, birth year, years of education, marital status and religion.
Standard techniques of survival analysis showed that the two groups of
siblings differed significantly in survival to older ages (see figure).
Survival rates were the same (relative risk= 1) at younger ages, but were
progressively higher for siblings of centenarians after age 70. By age
90-94, the relative risk for survival was 3.9 (95% CI: 3.2, 4.9) for the
female siblings of centenarians and 5.1 (95% CI:4.1, 6.4) for the male
siblings. Relative risks beyond age 90-94 continued to increase, but were
not statistically significant because of small numbers of subjects at these
extreme ages. For any age after 65, siblings of centenarians had a 42.4%
lower hazard of death (95% CI: 0.334,0.538,p<0.0005). Female siblings of
centenarians survived to a median age of 80 (95%CI: 79,85) and the males
survived to a median age of 76 (95% CI: 73,79), while female siblings of the
73-year-olds survived to a median age of 74 (95% CI: 69,77) and the males
survived to a median age of 73.5 (95% CI: 71,75).

Interestingly, we observed the centenarian probands had more siblings (4.5
siblings/ proband) compared to the seventy-three year old probands (3.2
siblings/proband). Several factors could have contributed to this finding.
Children whose parents were still alive may have been able to recall the
family pedigree better than the children of the septuagenarians who died in
1969. However we note that few centenarians assisted their children in
reporting data. There could also be some other hidden ascertainment bias,
although this seems less likely given the similarity in demographic
characteristics between the two groups of probands. In fact, it may well be
true that centenarians come from larger sibships. We (T.T.P.) recently
reported the finding that 19% of female centenarians had children after the
age of forty compared to 6% of women who died at the age of 73 years (1).
Perhaps relatively larger sibships occur in these families because there is
also an associated ability to have children later in life and therefore to
have more of them.
We have found that having a centenarian sibling increases one's chances of
survival to very old age, indicating a strong familial component to
longevity. Supporting evidence is provided by studies of old genealogies
(2). Although our study does not distinguish between shared environmental
and genetic factors, previous work suggests that genes may play an
increasingly more important role in achieving older and older age beyond
average life expectancy (3,4). A study of Danish twins thus appropriately
noted only modest heritability in the ability to reach the septuagenarian
years and slightly older, but significantly found no evidence for an effect
of shared family environment (5). While the twin study examined correlations
of age at death in subjects of average longevity, our study focused on
survival to extreme old age, and is therefore likely to detect a stronger
effect if familial factors play a greater role with increasing age. Further
work is needed to elucidate the contribution of genes to the familial
component of extreme longevity.
References to the Above Article:
1. Perls TT, Alpert L, Fretts R. Middle aged mothers live longer. Nature
1997; 339: 133.
2. Desjardins B, Charbonneau H. L'h ritabilit  de la long vit . Population
1990;3:603-616.
3. Bocquet-Appel JP, Lucienne J. La transmission familiale de la long vit   
Arthez d'Asson (1686-1899). Population 1991;2:327-347.
4. Rebeck GW, Perls TT, West HL, Sodhi P, Lipsitz LA, Hyman BT. Reduced
apolipoprotein epsilon 4 allele frequency in the oldest old. Alzheimer's
patients and cognitively normal individuals. Neurology 1994;44(8):1513-6.
5. M McGue, JW Vaupel, N Holm, B. Harvald. Longevity is moderately heritable
in a sample of Danish twins born 1870-1880. J Gerontol: Biol Sci
1993;48:B237-B244.
Relevant References:
1. Rebeck GW, Perls TT, West WL, Sodhi P, Lipsitz LA, Growdon J, Hyman BT.
The prevalence of apolipoprotein- E4 in very old Alzheimer's disease and
non-demented populations. Neurology, 1994;44:1513-1516.
2. Perls TT. Demographic selection's influence upon the oldest old. J
Gerontologic Psychiatry 1995;28:33-56.
3. Perls TT. The Oldest Old. The Scientific American, 1995;272:70-75. Perls
TT. The approach to the patient with cognitive impairment. Part 1:
Differential diagnosis. Clinical Geriatrics. April, 1995.
4. Perls TT. The approach to the patient with cognitive impairment. Part 2:
Management. Clinical Geriatrics. April, 1995.
5. Perls TT, Herget M. Higher respiratory infection rates on an Alzheimer's
special care unit and successful intervention. J Amer Geriatr Soc.
1995;43:1341-1344.
6. Gomez-Isla T, West HL, Rebeck GW, Harr SD, Growdon JH, Locascio JJ, Perls
TT, Lipsitz LA, Hyman BT. Clinical and pathological correlates of
apolipoprotein E epsilon 4 in Alzheimer's disease 1996;39:62-70.
7. Perls, TT, Wood ER. Acute Care Costs of the Oldest Old: They Cost Less,
Their Care Intensity is Less and They Go To Non-Teaching Hospitals. Arch
Intern Med 1996;156:754-760.
8. Perls T. Centenarians prove the compression of morbidity hypothesis, but
what about the rest of us who are genetically less fortunate? Medical
Hypothesis 1997;49:405-407.
9. Perls T. Apolipoprotein E and Its Association with Alzheimer's Disease.
Journal of Insurance Medicine 1996;2:114-118.
10. Perls T. Acute care costs of the oldest old. Hospital Prac
1997;32:123-137.
11. Perls T, Alpert L, Fretts R. Middle aged mothers live longer. Nature
1997;389:133.
12. Silver M, Newell K, Growdon J, Hyman BT, Hedley-Whyte ET, Perls T.
Unraveling the mystery of cognitive changes in old age: Correlation of
neuropsychological evaluation with neuropathological findings in the extreme
old. International Psychogeriatrics 1998;10(1):25-41.
13. Perls TT, Fretts, R. Why women live longer than men. Scientific American
Presents, June, 1998.
14. Perls TT, Bochen K, Freeman M, Alpert L, Silver MH. Validity of
reported age and centenarian prevalence in New England. Age and Ageing
1999;28:193-197.
15. Perls T, Alpert L, Wager CG, Vijg J, Kruglyak L. Siblings of
centenarians live longer. Lancet 1998;351:1560.
Book Chapters:
1. Alpert L, DesJardines B, Vaupel J, Perls T. Extreme longevity in two
families. A report of multiple centenarians within single generations. In:
Age Validation of the Extreme Old. Eds: Jeune B, Vaupel J. Odense Monographs
on Population Aging 4, 1998: Odense, Odense University Press.
2. Perls TT, Bochen K, Freeman M, Alpert L, Silver MH. The New England
Centenarian Study: validity of reported age and prevalence of centenarians
in an eight town sample. In: Age Validation of the Extreme Old. Eds: Jeune
B, Vaupel J. Odense Monographs on Population Aging 4, 1998: Odense, Odense
University Press.
Books:
Perls T., Silver M., Lauerman J. Living to 100: Lessons in Living to Your
Maximum Potential at Any Age, April, 1999. Basic Books, NY.

Mvh/Sincerely
Thomas Nord
Stockholm (Sweden)

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