Perspectives
Richard M. Friedenberg, MD
Longevity1
In the past, we have been told that life
is finite. There is a beginning and a
predictable end, which may vary in dif-
ferent individuals by some years. We
knew that life may be terminated by
disease at any age, but it was believed
that eventually, we all succumb to se-
nescence. It was always considered a re-
markable achievement to be a centenar-
ian, worthy of notice in newspapers and
even a congratulatory letter from the
president. However, the idea of a fixed
limit to life was always questionable,
since there is no known internal mecha-
nism that automatically terminates life.
In recent years, partly as a by-product of
the identification of the human genome
and the early success in gene manipula-
tion, we are now told that there may be
no finite end to life and that there may be
no such thing as death by senescence (1).
Our bodily systems attempt to preserve
life, and aging occurs because of the ac-
cumulation of myriads of tiny faults (1).
Death, then, is produced by treatable dis-
eases and therefore could be preventable.
Several decades in the future, the average
life span might be as high as 110 or 115
years.
For centuries, philosophers and phy-
sicians have searched for methods of
extending life span without success. In
Index terms:
Aging
Perspectives
Published online before print
10.1148/radiol.2233012153
Radiology 2002; 223:597– 601
1
From the Department of Radiological Sci-
ences, University of California at Irvine Med-
ical Center, Orange. Received January 14,
2002; accepted January 24. Address corre-
spondence to the author, 18961 Castle-
gate Ln, Santa Ana, CA 92705 (e-mail:
rmfriede@uci.edu).
© RSNA, 2002
the 16th and 17th centuries, death was
related to moral transgressions. Physi-
cians and philosophers believed that
Adam and Eve had been designed for
immortality and that their deaths were
the result of their moral transgression
of eating from the tree of knowledge of
good and evil (2). Despite this moral
transgression, according to the Bible,
Adam lived 930 years; his son Seth lived
912 years; and Methuselah set the bib-
lical record of 969 years. The vigor of
the human race appeared to diminish
after this, with Abraham living just 175
years (2).
Aging theories in the 16th and 17th
centuries revolved primarily around
moisture and heat (2,3). Living beings
were obviously warm, and the warmer
you were, the more vitality you had.
Dying individuals were colder and drier
and therefore closer to death. The com-
parison was made between the moist
and supple flesh of a baby and the wrin-
kled, dry, and leathery skin of an old
individual. It was believed that a longer
life might be obtained by preventing
the loss of heat and moisture, and this
was attempted by applying ointments
and oils to the skin and by limiting the
intake of food, since food and drink
required consummation of the body’s
innate heat. The body had a limited
supply of heat, and the more food you
consumed, the more heat was required
to consume the food. Shapin and Mar-
tyn, in their article “How to Live For-
ever, Lessons of History” (2), state that
there were skeptics even in those days
who questioned whether the practice
was worth the price. Michel Du Mon-
taigne, a philosopher of the time, was
skeptical about the promises made by
medical experts to prolong life. He be-
lieved the practice was not worth the
price and said, “If you follow the advice
of your physician, your life would be
miserable. Rather than extend life and
be miserable, live life and enjoy it” (2).
Similarly, in George Bernard Shaw’s
preface to The Doctor’s Dilemma (4), he
states, “Use your health even to the
point of wearing it out. That is what it is
for. Spend all you have before you die
and do not outlive yourself. Do not try
to live forever. You will not succeed.”
Despite the wisdom of these philoso-
phers, the search continued throughout
the centuries for methods to increase
longevity.
Guttman (5), quoting the report of the
Federal Interagency Forum titled “Older
Americans 2000,” noted that persons
born in 1960 have a life expectancy of
about 70 years (67 years for men; 73 years
for women), while for those born in
1997, the expected life span is 74 years
for men and 79 years for women. Persons
who reached the age of 85 in 1997 had
5.5 to 6.5 years of expected survival. Al-
though heart disease is still the leading
cause of death (40% for those over the
age of 85), there has been approximately
a one-third decrease in the rate of cardio-
vascular-associated lesions (3). Similarly,
the percentage of disabled elderly has de-
creased as preventative medicine such as
diet, vaccination, and mammography
has improved. Cognitive function has
also improved into older age. Among in-
dividuals between 65 and 69 years of age,
fewer than 5% displayed moderate or se-
vere memory impairment, which, as you
might expect, increases to 36% at age 85.
In Japan, the country whose citizens
have the longest life span, the expect-
ant life span is 75.9 years for men and
81.8 years for women (6). After reach-
ing age 65, the expected life span is 16.2
and 19.9 years, respectively. The same
numbers in the United States (5) are an
expected life span of 74 years for men
and 79 years for women, and after age
65, 14.9 and 19.1 years, respectively (7).
The Framingham Heart Program esti-
mated that by stopping smoking and
correcting blood pressure, cholesterol,
and obesity problems, those over the
age of 65 could add up to 5 years of life
expectancy (6).
597
 As people age, they seek remedies to
increase fitness and prolong life. Antiag-
ing medicine revolves around hormones
(estrogen, testosterone, and growth hor-
mones), vitamins, and herbal supple-
ments. Hormone levels decline with age,
and the appropriate level for a 65-year-
old is considerably less than that for a
25-year-old. The goal of antiaging medi-
cation is to restore the network of repair,
and there are those who believe that hor-
mone systems drive the maintenance and
repair systems of the cells. These sub-
stances are administered to approximate
what the body produces when it is func-
tioning optimally. They believe it restores
the antioxidant system to handle damages
from oxidative stress (8). Those who be-
lieve in hormone therapy will usually treat
those individuals in whom hormone levels
fall below 50% of the expected level in a
25–30-year-old. Growth hormone therapy
leads to a decrease in abdominal fat, an
increase in lean muscle mass, a decrease in
blood pressure, an increase in high-density
lipoprotein, and a decrease in low-density
lipoprotein; fasting insulin and glucose tol-
erance usually improve (9). They believe
that it helps prevent coronary artery dis-
ease and diabetes. As for herbal and vita-
min supplements, it has been estimated
that 60% of the individuals in New York
City over the age of 65 use them regularly
(10). Most reports of the beneficial effects
of herbal medication have been anecdotal,
but controlled studies are now being con-
ducted. So in essence, growth hormone,
testosterone, estrogen, vitamins E and C,
and herbal remedies are all in the package
of antiaging medications.
In 1996, the National Institutes of
Health Consensus Conference concluded
that the most modifiable risks are smok-
ing, high blood pressure, high blood lipid
levels, obesity, diabetes, and physical in-
activity. They stated that all Americans
should engage in regular physical activity
for at least 30 minutes at a moderate in-
tensity level every day of the week, since
physical inactivity was considered a ma-
jor risk for cardiovascular disease. About
one in four adults, more women than
men, currently live sedentary lifestyles,
and another third are insufficiently ac-
tive to achieve health benefits. This totals
approximately 55% of the population
(11) and occurs disproportionately more
among Americans who are less educated
and economically disadvantaged.
Since 1900, the number of persons
aged 65 and older has increased 11-fold,
while the number of those younger than
65 has tripled (12). Between 1965 and
1995, the older population increased by
598 䡠 Radiology 䡠 June 2002
82%, with one in eight Americans being
older than 65, and those 85 and older
(termed the oldest old) being the fastest
growing segment of the U.S. population,
reaching 31⁄2 million in 1994. Cassel (12)
estimates that in 30 years, one in five
Americans will be 65 years or older, and
the number over the age of 85 may ap-
proach 9 million. At the time this article
was written, the Social Security Adminis-
tration reported approximately 65,000
centenarians, with only 5,000 being
men. Cassel estimates that in 10 years,
there will be well over 100,000 centenar-
ians, and in 50 years, it may approach a
million. In the United Kingdom, people
over the age of 60 currently constitute a
fifth of the population and will consti-
tute a third by 2030. In the more devel-
oped countries as a group, by 2030 it is
estimated that people 65 and older will
constitute approximately 23% of the to-
tal population, and people 85 and older
will constitute approximately 6% (12).
There are many reasons for the in-
crease in life expectancy, and these could
be divided into environmental and ge-
netic reasons. Among the environmental
causes, medical progress would rank as
number one. Such items as the reduction
of premature death, the reduction of
childbirth-related deaths, the eradication
of serious infections, the decrease in
deaths from cardiovascular-related dis-
eases, the control of diabetes, and the
improvement of surgical techniques have
had a profound effect in that they in-
crease the potential of individuals to at-
tain older age. Other environmental fac-
tors include both behavioral and social
changes. These include a decrease in
smoking, the realization that diet and ex-
ercise decrease risk factors, and the estab-
lishment of Medicare in 1965, a major
factor in providing treatment for elderly
individuals. The major causes of death in
the elderly are heart disease, cancer, and
stroke, and the rates for each are about
the same at they were in 1965; the major
difference is that they are occurring at an
older age (12). Therefore, we are not so
much preventing these diseases as we are
postponing them. Senescence in itself is
not a cause of death, but a senescent cas-
cade of diseases that occurs in the elderly
may often be the cause of death. The
object should be to postpone disease as
long as possible and also to postpone the
onset of disability, which will provide a
shorter period of dependency before
death. McMurdo (13) believes that by
paying attention to three modifiable risk
factors— cigarette smoking, body mass
index, and exercise patterns—the onset
of disability could be postponed by
more than 5 years. Adapting such low-
risk habits can be associated not only
with an increase in life span but also
with an increase in health span. An-
other recognized risk factor for the el-
derly is hospitalization. Following hos-
pitalization, 30% of adults older than
70 lose the ability to perform at least
one of the activities of daily living, and
41% of these patients do not regain
their lost function over the next 3
months (12). These negative effects of
hospitalization must be combated with
earlier mobilization and a team ap-
proach to rehabilitation of the patient.
The other major factor affecting longev-
ity has been genetic analysis, which has
recently led to a revolution in aging re-
search. Researchers are continually search-
ing for genes that might influence life
span. The underpinning of the genetics
of aging relate to research conducted in
fruit flies and nematodes (14). Fruit flies
that exhibited the ability to reproduce
late in their life spans were selectively
bred over several generations, and this
group showed extended longevity. This
established the participation of genes in
aging. Single genes were found to modu-
late life span in the worm Caenorhabditis
elegans, a nematode that displayed in-
creased life span and led to the first iden-
tification of a longevity gene named Age
1, which remains to be cloned.
The relative importance of genetic in-
fluences on longevity was studied by
Ljungquist et al (15) and Wilmoth et al
(16), all from Sweden. Ljungquist et al
(15) followed a large sample of identical
and like-sexed fraternal twins together
with a subsample of 1,734 twin pairs
reared together and 130 twin pairs reared
apart that were born between 1886 and
1990. Their results suggested that the ge-
netic effect was small and that most of
the variance in longevity was explained
by environmental factors. Over the total
age range examined, they believed that a
maximum of about one-third of the vari-
ance in longevity was attributable to ge-
netic factors, and the remaining variance
was due to nonshared, individual, and
specific environmental factors (15). In-
vestigators who have analyzed trends of
mortality in Sweden since 1861 con-
cluded that of the total increase in max-
imum life span, the major portion was
due to a decline in mortality above age 70
(16). Other factors in order of importance
were the increase in number of individu-
als attaining old age, the increase in size
of the birth cohorts, and the reduction in
mortality before age 70.
Friedenberg
 Perls et al (17) suggest that extreme
longevity—living 20–25 years longer than
average—requires a genetic advantage.
This might include a decrease in genes that
are predisposed to disease, as well as the
presence of genes that slow the process of
aging and decrease the susceptibility to
age-related diseases. Investigators who
studied the siblings of centenarians identi-
fied a region on chromosome 4 in many of
the siblings that was highly suggestive of a
link to aging (18). It was suggested that
there are probably other genes that have a
similar effect and that there is probably a
small total number, such as four to six
genes, which have a major effect on lon-
gevity, although others believe that the
number may be substantially higher (19).
Over the past several years, the concept
of a fixed limit to human longevity has
become more questionable. Nearly every
system in the body does its best to pre-
serve life. Systems are not perfect, how-
ever, and aging occurs gradually from cel-
lular changes that accumulate over time.
Perhaps what we call senescence is the end
result of accumulated cellular changes.
I have addressed the question of lon-
gevity, but what about the quality of
those extra years? Although Americans
are living longer, is the quality of life
becoming better or worse after age 65?
Several investigators have approached
this question in an attempt to assess the
quality of life in elderly individuals
(5,20,21). The Federal Interagency Forum
on Aging, in their report titled “Older
Americans 2000: Key Indicators of Well
Being” (quoted by Guttman) (5), stated
that older Americans are living longer,
feeling better with less disability, and far-
ing better economically. Black and His-
panic Americans are still lagging behind
white Americans in this respect (5).
Persons who reached the age of 85 in
1997 had 5.5– 6.5 years of expected sur-
vival. However, aging gradually leads to
physical and mental deterioration. Heart
disease is the leading cause of death, with
cancer, stroke, chronic obstructive pul-
monary disease, pneumonia, and diabe-
tes as the next most frequent causes (3).
Five of these six diseases are chronic and
can produce severe disability. Arthritis af-
fects more than half the population aged
70 and older, followed by hypertension
(45%) and cancer (20%). In addition to
physical disability, moderate or severe
memory impairment increases with age.
At age 65– 69, fewer than 5% of individ-
uals display moderate or severe impair-
ment (only 1% severe); however, by age
85, this increases to 36%. Depression is
increasing and affects over 20% of those
Volume 223 䡠 Number 3
over the age of 85. Disability, defined as a
limitation of one of the activities of daily
living, affected over 7 million individuals
(21% of the population) in 1994 (3). In a
different study, next of kin were asked to
report on the use of hospitalization and
nursing home services in a large number
of deceased individuals who were aged 65
years and older in 1986. Results were
compared with those of a similar group
who were aged 65 years and older in
1993. They noted that women used sub-
stantially fewer hospital and nursing
home services in the last year of life in
1993 versus 1986, and men aged 85 and
older had a decline in nursing home
stays. The authors of this study con-
cluded that men and women over the age
of 85 experienced a better overall termi-
nal quality of life in 1993 than in 1986
(20).
A third study included 1,741 Univer-
sity of Pennsylvania alumni whose initial
data were accumulated in 1986 at an av-
erage age of 68 and who were then as-
sessed between 1987 and 1994 at the av-
erage age of 75. Investigators concluded
that persons with better health habits
survived longer and that disability was
postponed and compressed into a few
years at the end of life. This was not as
noteworthy for those with poor health
habits (21).
The overall impression is that the el-
derly population, in addition to living
longer, is living a better quality of life
than that of their predecessors some gen-
erations ago. Much of this relates to en-
vironmental changes that have produced
better health habits and that seem to
postpone the onset of disability, com-
pressing it into the last years of life.
Life span appears to be determined by
the interplay between environmental
and genetic factors. We can understand
the effect of environmental factors, but
how does genetic background influence
longevity? Are there specific genes that
increase longevity, or is longevity pri-
marily influenced by the genetic predis-
position to develop certain age-related
diseases? The answer to this question
may not be decided for many years. Some
authors believe that the main thrust is a
genetic predisposition to develop dis-
eases, allowing some individuals to either
delay or escape diseases associated with
aging (22). Even with a genetic predispo-
sition, however, there is considerable
variability among individuals with the
same genetic background as to when the
disease becomes manifest. For example,
the gene for polycystic kidney disease
may be present in members of a given
family, but some members of the family
may manifest the disease at age 22 and
others may not manifest the disease until
their 60s.
Holloszy (23) defines aging at the cel-
lular level as a progressive deterioration
of structure and function that occurs
over time. Primary aging refers to the de-
terioration of structure and function as a
direct result of the aging process. Second-
ary aging is that caused by diseases and
environmental factors. Improvement or
slowing of secondary aging can be de-
fined as an increase in average life span,
while slowing of primary aging results in
an increase in maximal life span. Hol-
loszy believes that there is a genetic pre-
disposition to develop age-related dis-
eases. He estimates that in mammals, the
genetic factor accounts for only about
35% of the interspecies variance in lon-
gevity. The rate of primary aging is prob-
ably genetically determined by the effec-
tiveness of mechanisms that act to
maintain structural integrity of cells in
tissues. These include protecting DNA
against free radical damage, repairing
damaged DNA, and providing protection
against the development of malignan-
cies. He believes that the genotypes that
are known to enhance longevity in hu-
mans do so with their influence on dis-
ease development. The achievements of
genetics in the analysis of aging in mam-
mals are less impressive than in other
organisms. So far, to our knowledge, no
genotype has been discovered that slows
the aging process in humans, although it
has been discovered in mice (24), nema-
todes, and fruit flies (14).
In 1990, there were 4 million people
aged 85 and older, the so-called oldest
old. It is estimated that there will be 40
million in 2040. Vaillant and Mukamal
(25) believe that it is not that individuals
are living longer, but that more people
are living to age 65. The life span of an
85-year-old man has increased by only
1.2 years, from 4 years in 1900 to 5.2
years in 1987. Therefore, the increase in
number of oldest old people directly re-
lates to more people reaching 65 years of
age. Both environmental and genetic fac-
tors have probably contributed to the
fact that elderly individuals report less
disability, and 40% of those over the age
of 85 remain fully functional. By using a
global definition of successful aging,
Vaillant and Mukamal (25) note that in
the Berlin Aging Study Cohort (26), at
age 75, 80% of the study population were
still considered in good health, cogni-
tively fit, active, and involved in life, or
in average health, still independent, and
Longevity 䡠 599
satisfied with life. At age 95, this level of
health was maintained by only 30%. Two
of the most important psychosocial pre-
dictors of successful aging were high level
of education and having an extended
family network. After age 30, our ability
to recall proper names steadily declines,
but such anomia does not predict de-
mentia.
In 1948, the World Health Organiza-
tion defined health not as the absence of
illness but as the presence of physical,
mental, and social well-being (27). Inves-
tigators in study at Harvard University
followed two socially diverse cohorts of
adolescents, one a college group and the
other a core city group, until they be-
came great-grandfathers (25). They were
all males from the United States, and all
were white. The college cohort reached
every stage of disability and death about
10 years later than did the core city
group. At age 65, 25% of the core city
group were dead, and 20% were disabled.
At age 75, 27% of the college men were
dead, and 14% were disabled. Obviously,
education, which includes a certain de-
gree of affluence and access to health,
made a substantial difference. Predictor
variables change over time. Serum cho-
lesterol level, for example, may be impor-
tant in the young, but in the elderly co-
horts after age 70, it may not be a general
risk factor (25). Shortened ancestral lon-
gevity is a risk factor for people who die
before the age of 60, but it may not be a
risk after that age (25).
What effect will longevity have on
health care costs? In the United States,
people 65 years of age or older are pro-
jected to increase from 13% of the popu-
lation in 2000 to 20% by 2030 because of
the aging of the baby boom generation
and increased longevity (28). As the 85-
year-old population increases, they are
more likely to require nursing home care,
and currently, Medicaid pays about half
of the total costs of nursing home care in
the United States. As might be expected,
as the age at death increases, the propor-
tional expenditure for acute care de-
creases and that for nursing home care
increases. On the basis of Medicare data,
Spillman and Lubitz (28) state that the
total projected expenditure for all ser-
vices from the age of 65 years until death
in 1996 dollars was $164,505 per person.
Of this amount, the bulk was for Medi-
care ($105,342) and for nursing home
care— care not covered by Medicare
($34,205). Nursing home costs increase
with patient age. Average nursing home
costs were $12,000 for those who died at
age 75 and $64,000 for those who died at
600 䡠 Radiology 䡠 June 2002
age 90. Nursing home costs surpass Medi-
care costs for persons older than 97 years.
The authors estimate that for all individ-
uals born in 1950 who turn 65 in 2015,
health care costs in 1996 dollars will be
73% higher than the combined expendi-
tures for individuals who turn 65 in
2000. This assumes that Medicare rates
remain the same and that insurance cov-
erage remains more or less the same. The
most important factor is the higher num-
ber of persons projected to reach age 65
in 2015. It is estimated that 47% of per-
sons who reach age 65 in 2015 will sur-
vive to age 85.
Throughout this article, I have tried to
establish two different but intimately re-
lated concepts. The first is the increase in
longevity, and although the projections
that I have quoted are all individual con-
cepts, there is no doubt that there will be
real increases in the future. It is possible
that average life span will increase to 90
or 95 years in the next few generations
and that 5%–10% of the population may
reach the century mark. The second re-
lated concept is the quality of life, and
this is much more difficult to project.
Even if death is not related to senescence
but is due always to disease, and if in-
creased longevity is related to the delay
of onset of diseases, will most of the in-
dividuals older than age 90 be confined
to wheelchairs, perhaps with severely
diminished cognitive qualities? Perls et al
(29), reporting on a population of 460,
829 in a New England centenarian study,
noted that 8,856 (1.9%) were older than
age 85, and among them, 46 were veri-
fied centenarians, a ratio of one per
10,000. Of this group, 61% were in nurs-
ing homes. He projected that by 2000,
there may be as many as 100,000 cente-
narians worldwide.
In addition to physical disabilities, the
incidence of dementia appears to in-
crease dramatically with age. In one
study, dementia has been reported in 1%
of the population at age 65, increasing to
47% by age 85 (30). Investigators in a
Canadian study noted that the preva-
lence of dementia rose from 40% among
those 90 –94 years old to 59% among
those 95–99 years old (31). There have
been insufficient data on those over 100
years old. Rose (32) believes that al-
though we may delay death, we will not
be able to markedly delay, beyond what
has already been accomplished, the de-
cline in physiologic function. He believes
that people will live longer but will not
enjoy much more of a robust old age
than their counterparts of previous gen-
erations.
We have unquestionably increased the
quality of life for individuals under the
age of 90 by means of social and environ-
mental factors discussed previously. It
may be more difficult to avoid the phys-
ical and mental deterioration of those
older than 90 years. Aging research
promises marked progress, but this has
not been matched by equal progress in
improving quality of life. Prolonged in-
firmity may be the fate of most of those
older than 90 years. In the Berlin aging
study, only 30% of those older than 90
years were in reasonable health (26). If
this continues, we will not have accom-
plished much. We would all like to live as
long as possible, but we must balance this
with the quality of life obtainable. Dis-
ease and death will be with us forever.
The interpretation of the quality of life
will vary between individuals, but if we
cannot improve it, what have we really
accomplished by extending life? Those
focused on prolonging life through ge-
netic and environmental research must
also focus on improving the quality of
those added years to make their work
meaningful.
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