FUTURE HISTORY
Journal of Gerontology: MEDICAL SCIENCES
2003, Vol. 58A, No. 2, 138–145
Copyright 2003 by The Gerontological Society of America
The Aging–Disease Dichotomy:
True or False?
Herman T. Blumenthal
Division of Geriatric Medicine, Department of Medicine, Saint Louis University School of Medicine, and the Aging and
Development Program, Department of Psychology, Washington University, St. Louis, Missouri.
Aging and disease are not synonymous. There are
processes of aging and etiologies of disease. The
relationship between the two are important, but not
inevitable. (1)
. . . to draw a distinction between disease and
normal aging is to attempt to separate the undefined from the undefinable. (2)
ISTORIES of gerontology recount that centuries
H
before there there was a formal concept of biological
aging or of definitive disease in its modern context, some
philosophers and statesmen held opinions as to the nature of
death in old age. Following are two examples that are
particularly relevant to the subject of this essay.
The death that comes in old age is painless, for the
aged die without any violent affection befalling
them, and the parting of their soul is quite unfelt.
(Aristotle, On Respiration)
Yet it may be urged, many old men are so feeble
that they can perform no function that duty or
indeed any position in life demands. True, but that
is not peculiar to old age: generally it is
characteristic of ill-health. . . . Old age is an incurable disease. (Cicero, De Senectute)
Back then, most of what we now regard as manifestations
of biological aging consisted of its external anatomical and
behavioral manifestations. The earliest recorded descriptions of definitive disease (during the Medieval–Renaissance period) consisted of incidental observations in the
course of anatomical dissections. Ancient anatomists such
as Vesalius, Leonardo de Vinci, Benvieni, and Serino were
able to record only gross anatomical manifestations of the
aging-associated diseases, including gangrene of the lower
extremities; cancer of the stomach, large intestines, and
bladder; and the tortuosity and hardening of the arteries that
we now subsume under the term arteriosclerosis.
With the advent of the microscope and the emergence
of cellular pathology as a science, the autopsy became an
almost routine postmortem procedure. The European
founders of this discipline, such as Virchow, Rokitansky,
Aschoff, Morgagni, and others, added descriptions of both
gross and microscopic characteristics of diseases such as
arteriosclerosis, myocardial infarction, patterns of metastases in cancers, cirrhosis of the liver, degenerative diseases
of the joints, osteoporosis, endocrine disorders, vascular
aneurysms, and senile amyloidosis. It was Virchow, in
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particular, who noted that all diseases are, in the final
analysis, traceable to large or small groups of cells, the
functional capacity of which is altered in accordance with
the state of their molecular composition.
Despite these early anatomical observations of definitive
pathological lesions, the late-18th-century publications on
the theory of medicine by William Cullen at the University
of Edinburgh Medical School in Scotland revealed that
the clinical classification of disease was based solely
on symptomatology. Concepts of disease etiology did not
emerge until the late 19th and early 20th centuries,
following the discoveries of Pasteur, Koch, and others that
specific microorganisms cause particular diseases. Definitive proof of etiology was based on the verification of
Koch’s postulates—the injection of a pure culture of the
suspected microorganism into animals, and the demonstration that these animals develop a disease comparable with
its human counterpart.
There followed recognition of the fact that malignancies
can be induced by viruses, by the application of carcinogenic chemicals, or by exposure to radiation. Also during
this period, Anitchkow demonstrated that animals fed a highfat diet displayed vascular lesions similar to those of
humans, later designated by the term atherosclerosis. These
observations gave rise to the concept of disease etiology that
we now call the medical model.
The concept of an aging-disease continuum seems to have
been considered by Claude Bernard as early as 1865 (3), as
evidenced by the following statement:
We shall never have a science of medicine as long
as we separate the explanation of the pathological
from the explanation of normal vital phenomena.
Although the foregoing provides a historical account of
opinions regarding an aging–disease relationship, it also
continues into the modern era. In addition to the contrasting views of Shock and Evans, an appendix at the end of
my essay provides a diversity of opinions by others on the
aging–disease relationship (4–29). These are classified as
to whether they are in accord or in opposition to an
aging–disease dichotomy, or whether they are ambiguous in
this regard.
In keeping with the sectional division by disciplines
represented in The Gerontological Society of America
(GSA), the authors of these statements include biologists,
physicians, psychologists, and social scientists. The dates
provide a time frame that stretches from the advent of the
medical model over a century ago to the present time.
FUTURE HISTORY
Although this is by no means a complete list of those who
have made statements regarding this conundrum, the
number of authors in each category is, nevertheless,
indicative of the fact that the spectrum of views has not
changed substantially over the course of the past century.
Furthermore, a reading of these statements provides a variety
of reasons on which opinions have been based.
THE MODERN CONCEPTUALIZATION OF A DICHOTOMY
In the early years of the GSA, over a half-century ago,
two slogans dominated the discourse—‘‘The (singular)
aging process,’’ and ‘‘aging is not a disease.’’ The first
was based on the belief that a single mechanism would
eventually be discovered that would account for the many
and varied manifestations of aging. Since it later became
clear that there was no single molecular or cellular cause of
aging, this view was abandoned. However, the singular
expression is still frequently encountered.
Over a half-century ago, Strehler (7) offered the
following five criteria posited to distinguish biological
aging from aging-associated diseases: intrinsicality, universality, irreversibility, progressivity, and genetic programming. Several of these criteria were subsequently abandoned
in recognition of the diversity of the manifestations of
biological aging, the fact that manifestations of aging are not
genetically programmed (in fact, aging is associated with
genetic instability), and the fact that diseases (as is the case
in biological aging), if cures are not available, are
progressive and irreversible. Acknowledging the fact that
defining biological aging is difficult, other authors (30,31)
offered a less restrictive definition—biological aging as the
result of failure of homeostatic systems, resulting in an
increasing probability of death.
Intrinsicality and Universality
Although a 1996 symposium on aging theories as applied
to all of the subdisciplines of gerontology (32) acknowledged the fact that there is no definitive theory of aging,
Strehler’s criteria of intrinsicality and universality merit
attention because they might serve as a basis for distinguishing between biological aging and aging-associated diseases.
Intrinsicality remains important for those who believe that
aging-associated diseases derive from extrinsic causes in
accord with the above-noted medical model. Opposing this
concept is the view that there are intrinsically generated
phenomena that can account for both biological aging and
aging-associated diseases. Universality in regard to biological aging and aging-associated diseases can be applied
in two ways—across species or within species. As to biological aging across species, Finch (33) provides the following observation:
(There is) an enormous range of rates . . . There
are species that may experience negligible degrees
of senescence in certain environments, and some
in which advanced age may not compromise
reproductive function.
Although biological aging may be universal in mammalian species, it has also been argued that no single disease
139
can account for the termination of the life span in all aged
individuals, although coronary and cerebrovascular disease,
cancer, and dementia, taken together, may approach
universality. Furthermore, there are autopsy studies that
suggest that amyloidosis alone may approach universality in
very old subjects (34).
The expression ‘‘aging is not a disease’’ may have
initially been based as much on the objective of establishing
aging as an independent discipline as on the existence of
convincing evidence that aging and aging-associated
diseases are separable entities. Be that as it may, the
separation of biological from pathological aging is based on
the following tenets. First, any disease during the lifetime of
an individual is capable of adding ‘‘injury’’ to the ‘‘insult’’
of biological aging. Second, certain diseases have a high
prevalence among the aged population because the offending extrinsic agent(s) produce disease after a long latent
period, or because repeated insults are required. Third, the
diseases with a high prevalence in the aged population are
the consequence of the aging-linked weakening of critical
biological defense mechanisms, which then permit the
effects of extrinsic agents to take hold.
THE CONUNDRUM OF CAUSALITY
For over a century, concepts of disease causation have
undergone an evolutionary process. It began with Koch’s
postulates that provided the infectious disease model while
recognizing that the immune system could provide protection. Like the infectious disease model, the current
medical model holds that the immediate causes of noninfectious diseases are also of external origin. In regard to
aging-associated diseases, the above-noted tenets hold that
they are caused by unspecified external agents in combination with an aging-related waning of defense systems to
confer susceptibility.
The Morass of Risk-Factor Etiology
Because definitive causal agents comparable with those
that are operative in infectious diseases are not applicable,
so-called risk factors have become popular proxies for
causation. Hill (35) has listed a number of criteria for
validating a causal link that extends beyond a statistical
correlation. In the context of the causation of agingassociated diseases, the following questions appear to be
particularly relevant: Does the causal relationship make
biological sense? Is it at least biologically plausible? Is the
causal association compatible with present knowledge of the
disease?
There are examples of correlations that comply with
these criteria and others that do not. The risk factors most
commonly studied include dietary indiscretions, obesity,
tobacco consumption, a sedentary lifestyle, and exposure to
harmful environmental pollutants and insecticides. An
example of the latter are the estrogenic effects of some
pesticides with the potential for causing mutations leading
to several types of human cancers (36). As to other causal
relationships that make biological sense, tobacco consumption has been statistically linked with lung cancer, and it
makes sense in that tobacco tars are mutagenic. However,
the majority of lung cancers occur in nonsmokers. Obesity
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BLUMENTHAL
and hyperlipidemia are statistically associated with some
types of diabetes, and this association can be explained on
the basis of their metabolic link with insulin resistance.
Studies on the beneficial effects of exercise have
been questioned on the basis that those who exercise may
be healthier at the outset than those who do not (37). In
addition, although the short-term benefits of exercise are
clear (38,39), there is a question of whether these benefits
can be sustained (40).
In contrast, studies by sociologists have revealed that the
effect on mortality of low socioeconomic status is greater than
that of such risk factors as cigarettes, hypertension, and
hypercholesterolemia combined. In this regard, the mortality
gap between the rich and poor has been growing wider (41).
There are confounding features that also have to be
considered. One disease may serve as a risk factor for
another, such as hypertension or diabetes for heart disease
and stroke. Furthermore, some risk factors are associated
with more than one disease; for example, smoking cigarettes
is associated with experiencing both heart attacks and
cancer, diseases that have little in common in their
pathogenesis. In contrast, some of the risk factors linked
with coronary artery disease do not apply to cerebrovascular
disease, although the two are similar in their pathogenesis.
Some correlations do not survive the test of time.
Recommendations based on earlier observational studies
on hormone replacement therapy in postmenopausal
women, most lacking randomized control clinical trials,
have had to be revised because a later more comprehensive
study proved them to be in error. On the basis of earlier
findings it was concluded that estrogen therapy in
menopausal women would reduce the risk of coronary
artery disease but increase the risk of breast, endometrial,
and cervical cancer. The risk of these cancers could be
reduced by using a combination of estrogen and progesterone. A more recent randomized control study (42)
involved 16,608 postmenopausal women aged 50–79 years
with intact uteri who were tested in a study using a placebo
compared with an estrogen–progesterone mixture design.
The study was halted after a mean of 5.2 years because of
the increased risk of breast cancer despite or because of the
inclusion of progesterone. Moreover, it also showed an
increased risk for heart attacks, stroke, and pulmonary
embolism. Similar correlations have been drawn between
low testosterone and loss of muscle mass and cardiovascular
disease in older males (43–46). This condition of andropause represents a classical example of the disease-aging
continuum, with longitudinal studies showing a fall in
testosterone levels in all men (47), but treatment studies
suggesting that it is only at disease levels of testosterone that
symptoms occur and are reversed by treatment (48–50).
There is a major need for a Men’s Health Study similar to
the Women’s Health Initiative to determine the validity of
these claims.
Current risk assessment is, in a sense, a throwback to the
period when disease was attributed to the cumulative effects
of a variety of harmful environmental factors. An important
difference now, however, is that risk assessment is disease
specific and based on clinical criteria. In these actuarial
times, statistical correlates have become the new ciphers for
disease phenotypes. To emphasize the absurd lengths to
which some correlations have been carried out, McCormick
noted in a 1993 report (51) that over 300 risk factors have
been associated with coronary heart disease.
Statistical analyses are also often incomplete because they
do not distinguish between the causal connection as
a necessary one comparable with an infectious agent, or
one that only confers susceptibility. In diseases with age
at onset in the senescence period of the life span, it is
particularly important to distinguish between direct causal
mechanisms and the indirect impairment of defense
mechanisms.
With regard to aging-associated diseases, chronological
age provides the strongest statistical correlate. Moreover,
Forbes and Gentleman (52) have identified putative similar
pathways between smoking-induced life shortening and
biological aging, suggesting that smoking may, in effect, be
an accelerator of aging.
Genetic Risks
In lieu of risk factors, Williams (53) stresses the role of
germline genetic factors, and he notes that only ;20% of
cigarette smokers develop lung cancer whereas the mechanisms that protect the other 80% remain largely unknown.
Familial aggregation has been observed for disorders such
as cardiovascular disease and cancer. Of men with coronary
heart disease occurring before the age of 55, 50–60% have
a strong family history of this disease. With regard to
hypercholesterolemia, although the inherited forms represent only ;5% of the general population, they account for
more than 50% of cases with onset before the age of 55.
Total cholesterol as a risk factor for cardiovascular disease
progressively declines with advancing age, and in those
over 85, high cholesterol concentrations are associated with
longevity (54), although the prevalence of coronary heart
disease continues to rise in this group of advanced age.
In sum, the determination of causality involves complex
processes, whether applied to biological aging, to risk
factors, to genetic determinants, or to aging-associated
diseases. The further identification of single nucleotide
polymorphisms (SNPs) linked with particular disorders
should provide additional information regarding genetic
risk. It may even be that the diseases with age at onset
during the senescence period of the life span involve fewer
complexities, because the role of risk factors and of genetic
risks plays a progressively diminishing part with advancing
age, and the oldest old appear to represent an elite
population relatively invulnerable to these risks (55).
Nevertheless, the prevalence of these same phenotypic
diseases continues to rise in the oldest old, because, as
noted elsewhere (56), the advent of techniques for
analyzing the molecular biopathology of aging and agingassociated diseases has led to the conclusion that more than
one pathogenetic pathway may lead to the same phenotypic lesion.
THE RELEVANCE OF LONGEVITY EXTENSION TO A
RESOLUTION OF THE AGING–DISEASE DICHOTOMY
Longevity extension, also regarded as a retardation of
biological aging, might be viewed as an opportunity to
FUTURE HISTORY
clarify the aging–disease relationship. There are three major
lines of activity directed at either extending human
longevity or at identifying determinants of the human life
span. The first, as noted by Olshansky and colleagues
(12,57), and in an editorial in the Journal (58), is an illconsidered expansion of hormone replacement therapy
conducted under the auspices of The American Academy
of Anti-Aging Medicine. It promotes the administration of
such agents as pituitary growth hormone, testosterone, and
adrenal dehydroepiandrosterone (DHEA), despite the possibility that there may be harmful consequences comparable
with those already noted with regard to hormone replacement therapy in menopausal women.
The second is a study conducted by Perls (59), the goal of
which is to identify the genetic and phenotypic markers
characteristic of centenarians. The third line of activity
consists of the ongoing studies on longevity extension by
caloric restriction (CR) in rodents, but now also extended to
primates (60–63).
The changes in CR rodents associated with increased
longevity, some of which are also present in centenarians
and tentatively in CR primates, include a reduction in
triglyceride and melatonin levels, in oxidative damage, in
glucose tolerance, in plasma insulin, and a reduction in the
rate of decline in DHEA. The search is already on for an
antiaging pill that would have effects similar to CR and be
more acceptable to humans (64).
In a review of CR studies that extend the life span of mice
and rats, Masoro (65) has concluded that CR does not
eliminate aging-associated diseases; it only postpones their
age at onset, thereby providing support for the role of
reactive oxygen species and advanced glycation end (AGE)
proteins in the generation of diseases in this model, albeit at
a slower rate (66).
In presenting studies dealing with genes that can be
manipulated to extend longevity in yeast, Caenorhabditis
elegans and Drosophila melanogaster, Guarante and
Kenyon (67) further blur the distinction between biological
aging and aging-associated diseases. They state:
When single genes are changed, animals that
should be old stay young. In humans these old
mutants would be analogous to a ninety year old
who looks and feels forty-five. On this basis we
begin to think of ageing as a disease that can be
cured or at least postponed.
Conclusions
First an explanatory note on terminology. In this essay I
have used the term aging-associated disease rather than
age-related disease. This choice is to emphasize that the
primary focus here has been on diseases with age at onset in
the senescent period of the life span, the oldest old, rather
than through progressive periods of the total life span.
In considering the basis for a separation of the
degenerative changes in ‘‘normal aging’’ from an agingassociated disease, how does one define a disease?
Philosophers, ethicists, clergy, social scientists, and physicians have wrestled with this definition (68). Some define it
as a default value—the absence of a state of proper or ideal
141
functioning. Others regard disease as any condition
associated with discomfort, pain, disability, or death—or
an increased liability to these states. By some of these
criteria, even ‘‘normal aging’’ would qualify as a disease.
How, then, does one distinguish between a biological
aging lesion and a disease?
For the dichotomists, the challenge is to delineate
a defineable border that separates biological from pathological aging. Although the notion of a dichotomy between the
two dates from antiquity, in the modern era it dates from
approximately 1929 to the present. Most recently, it has
been addressed by Olshansky and coworkers (12,57). They
comment as follows (57):
Until we better understand aging processes and
discover how to manipulate them, these intrinsic
and currently immutable forces will continue to
lead to increasing losses in physiological capacity
and death, even if age-associated diseases could be
totally eliminated. (p. B293)
Nothing is really new here. Of the criteria proposed in the
modern era of gerontology for separating biological from
pathological aging, Olshansky and colleagues again apply
the criteria of intrinsicality and universality—and ultimately
a biological death at the end of the life span in the absence
of disease.
In this paradigm, what are the causes of disease?
Because direct causation in compliance with the Pasteur–
Koch model is not applicable to noninfectious degenerative
diseases, the medical model presently in vogue employs
risk factors as proxies for the extrinsic causation of agingassociated diseases—accompanied by germline genetic
risks. Although there may be applications in which the
risk factors make biological sense and germline mutations
have been identified as causal, they are not applicable to
the causation of the degenerative diseases of the oldest
old. As Perls (55) has recorded, the oldest old, including
centenarians, have escaped the risk factors and genetic
risks, whereas the prevalence of aging-associated diseases
continues to rise.
For those supporting a continuum between the two, it is
necessary to delineate the paths leading from a biological
aging phenomenon to a disease. In short, we must demonstrate that aging is not simply just another risk factor for
disease, but that the two are more intimately connected. A
resolution of this conundrum rests on the identification of
disease causation in the context of biological aging.
What has changed the dialogue between those supporting
a dichotomy and those supporting a continuum are concepts
that have evolved in the modern era of gerontology with the
potential for linking the two. As more knowledge about
aging has been acquired, it has become evident that the
manifestations of biological aging are so diverse that they
cannot be attributed to one or only a few causes, thereby
blurring the distinction between biological and pathological
aging of possible intrinsic origin. A classical example is
frailty, which appears to be a combination of multiple
diseases leading to a decline in functioning (69–72). A
paradigm shift in concepts of biological aging took place
with the advent of the stochastic theory of biological aging.
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Particular landmarks include Harman’s demonstration of the
effects of intrinsic free radical generation (73), followed by
Cutler’s (74) introduction of the concept of intrinsic errors
in transcription, translation, and posttranslational modification of proteins; and, related to the generation of free
radicals, the role of AGE products by Brownlee and
associates (75). These advances provided the basis for
a continuum between biological and pathological aging.
Holliday (18) subsequently provided a list of causes and
defenses of biological aging that apply equally to the
intrinsic genesis of aging-associated diseases.
Senile amyloidosis is a long-recognized phenomenon in
both rodents and humans (76). Its genesis has recently been
identified as a posttranslational misfolding of proteins (77).
Amyloidosis is generally recognized to be a disease, and
autopsy studies (34) place its prevalence at 80–100% in
subjects of advanced age, thereby approaching universality.
A major cause of Alzheimer’s disease is thought to be
overproduction of beta-amyloid. An animal model of betaamyloid overproduction, the SAMP8 mouse, has early
memory disturbances directly attributable to beta-amyloid
overproduction, but in many ways it otherwise resembles
senescent mice (78–81).
There are other relevant connections between biological
aging and disease that support a continuum. Two examples
follow: the first is based on a homeostatic system gone
awry, and the second is based on events linked to the
stochastic concept of biological aging. First, people who
develop type 2 diabetes pass through three phases. The
first phase, as demonstrated by the Baltimore Longitudinal Study (82), is the long-recognized biological aging
phenomenon in which there is a progressive deterioration
in glucose tolerance with advancing age. It then may
progress to a state designated as ‘‘impaired glucose
tolerance’’ and insulin resistance. In a final progression,
overt diabetes emerges. Accompanying this process is
a progressive increase in the production of AGE proteins that gives rise to the vascular complications of
diabetes (83). Second, Ames and associates (66) argue as
follows:
Metabolism, like other aspects of life, involves
tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein and
lipid. We argue that this damage (the same as that
produced by radiation) is a major contributor to
aging and to degenerative diseases of aging such as
cancer, cardiovascular disease, immune-system
decline, brain dysfunction and cataracts.
Is the dichotomy issue only a philosophical one, or will
its resolution have consequences? Hayflick calculates (11)
that successful eradication of cardiovascular and cerebrovascular disease and cancer would add only 15 years to
our average life expectancy. Although eradication of these
diseases has yet to appear on the horizon, the studies on
longevity extension in rodents, now extended to primates,
indicate that this strategy would postpone these diseases to
a later age at onset, but not eliminate them. In addition,
although the effect on disease (postponement or elimination) of an antiaging drug that would mimic CR are not
known, there are serious reasons to question the advisability of the longevity extension enterprise.
As documented in a previous essay (56), it has been
projected that, even without a longevity extension program, by the year 2050 we will have approximately 70
million Americans over the age of 65 and approximately
50 million over the age of 85. Centenarians will number
around 300,000, and they would still be dying of disease,
not of old age. According to Kevles (84), ‘‘elderly women
will make up a disproportionately large fraction of society,
and our society will be burdened with a huge cadre of
people beyond reproduction or work.’’ Disease prevention
using already available knowledge appears to decrease
morbidity associated with aging (85). Our system for providing for the health care needs of the aged population is
already under severe stress, and future planning should
place a much higher priority on providing for an even
larger population of the aged than on extending the human
life span and further intensifying this problem.
ACKNOWLEDGMENT
Address correspondence to Herman T. Blumenthal, 6203 Washington
Avenue, St. Louis, MO 63130.
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Received September 9, 2002
Accepted September 11, 2002
APPENDIX
In Accord With a Dichotomy
‘‘Death from senescence alone can occur.’’ (4)
‘‘To me, ‘pathological’ actually means something which
is added on to the normal changes in the life history of an
organism.’’ (5, p. 81).
‘‘If aging is an illness, this is true only in the sense of its
limitations rather than the purity of its syndromes
susceptible to special medical influences. In this view it
can be concluded that the forces of aging are not a sickness
in the accepted sense of the word, but that aging is
irreversible. . . .’’ (6)
‘‘These three events (coronary artery occlusion, cerebrovascular accident, the initiation of a tumor) which incidentally account for the majority of deaths in the older age
group in Western countries, are not themselves considered
to be part of the aging process even though they might occur
universally.’’ (7)
‘‘Of the letters and editorials you (The Lancet) have
published on aging, none explains the difference between
aging phenomena (genetically programmed) and ageassociated pathological phenomena (acquired or initiated
by external events). This distinction must be made or there
will be no progress.’’ (8)
‘‘On the one hand we must distinguish between aging and
disease; on the other hand the interaction between them is of
considerable and theoretical interest. . . .’’ (9)
‘‘The term ‘biological aging’ should, in my judgment, be
reserved for characteristics and processes that occur
universally with aging in all members of a given species.
Conversely, factors that impinge upon and influence aging
in varying degrees, separate from the universal genetically
programmed factors, include lifestyle factors, exposures to
environmental influences, and disease.’’ (10)
‘‘Advances in our knowledge of age-associated diseases
have far outpaced advances in our understanding of the
fundamental ageing processes that underlie the vulnerability
to these pathologies. If we are to increase human life
expectancy beyond the fifteen year limit that would result if
today’s leading causes of death were resolved, more
attention must be paid to basic research on ageing.
Determination of longevity must be distinguished from
ageing to take us from the common question of why we age
to a more revealing question that is rarely posed; why do we
live as long as we do? But if the ability to intervene in
ageing ever becomes a reality, it will be rife with unintended
consequences.’’ (11)
‘‘Aging, in our view, makes us ever more susceptible to
such ills as heart disease, Alzheimer’s disease, stroke and
cancer, but these age-related conditions are superimposed
on aging, not equivalent to it.’’ (12)
In Accord With a Continuum
‘‘The textural changes which old age induce in the
organism sometimes attain such a point that the physiological and pathological states seem to mingle by an
imperceptible transition and to be no longer sharply
distinguishable.’’ (13)
‘‘It is my conviction that death in human beings never
occurs, or only in rare instances, without pathological
changes to which death might be attributed. . . . Autopsies
which have been made in the very old always show
a pathological cause (of death).’’ (14)
‘‘Can the effects of aging be distinguished from those of
pathology? To attribute to aging all time associated changes
to which no specific cause can be found is at best
a temporary holding tactic which will suffice only as long
as we are ignorant of the mechanism involved. Time alone
causes nothing.’’ (15)
‘‘. . . man will never die of old age but always from
disease. However, terminal disease of the future will be
different from that we are faced with now and presumably
more diversified.’’ (16)
‘‘Attempts have been made by numerous workers to
separate physiological from pathological aging. The two are,
however, so interrelated as to make attempts relatively
abortive. It would be far more relevant to accept the
existence of a continuum of ageing phenomena.’’ (17)
‘‘. . . the distinction between so-called natural ageing and
the pathologies that are common in old people is artificial.
What we see is an increasing likelihood of many diseases in
individuals as they age, which does not, of course, mean that
all individuals develop all the pathologies.’’ (18)
‘‘If one defines disease as ‘reaction to injury’ there is no
clear distinction between aging and other diseases.’’ (19)
‘‘. . . we are told at the outset that we should focus on
distinguishing changes in the elderly due to disease or
disease from changes due to true aging, thus the ‘usual
versus successful’ ideology was imposed a priori. What if
the ‘aging vs disease’ dichotomy is an unsuccessful way of
conceptualizing research problems in gerontology?’’ (20)
‘‘Although it is well known that most diseases show
marked increases with age, the connection between the
ageing process and the incidence of age-related diseases is
highly underestimated. Recent developments in gerontology
FUTURE HISTORY
are unearthing the molecular link between ageing and
disease.’’ (21)
Ambiguous Views
‘‘Research to control aging and to treat aging will,
whether we like it or not, turn aging into a disease—for if
aging or death occur at a time when it could have been
postponed, it comes to be regarded as a disease.’’ (22)
‘‘Why do we die? Although manifest senescent disease is
primarily a medical problem, its roots are biological, and the
intractability of the problem of death arises from the
difficulty of bringing the immense variety of clinical and
pathological phenomena into relation with the parsimonious
thought processes of biological science.’’ (23)
‘‘The diseases with which large numbers of aging
individuals die can be classified in three ways in regard to
aging: 1. Diseases that are aging processes themselves. 2.
Diseases that show an increasing incidence with age. And 3.
Diseases that have more serious consequences with increasing age.’’ (24)
‘‘. . . there is no reason in principle why some of the
disagreeable changes that accompany aging should not be
diminished or annulled—particularly those which are
clearly secondary in nature. These are physical changes,
145
no different in principle from other disease processes and no
less amenable to investigation and treatment.’’ (25)
‘‘Autopsy studies indicate that the concept of pure
physiological aging as a cause of death is observed rarely,
if ever, and that with age the individual shows an increasing
number of organic lesions of the cardiovascular, cerebral
and other systems. Thus as far as can be foreseen, extension
of the life-span depends essentially on retardation of
pertinent pathological processes.’’ (26)
‘‘In the future studies of aging must better attempt to
capture the interplay between diseases and aging phenomena.’’ (27)
‘‘Many basic factors about senescence in even the best
studied specimens are still being revised as the multifarious
confoundings of age-related diseases are best understood. It
is noteworthy diseases of adult humans have been
considered in isolation from the larger manifold of changes
in this age group; this narrow view may have limited
progress.’’ (28)
‘‘Scientific evidence is rapidly accumulating to suggest
the hypothesis that the fundamental age-related changes that
ultimately result in the functional deficits, pathologies and
diseases of the aged are based, in part, on specific agerelated changes in gene expression.’’ (29)