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OCR for page 10
Aging and Environmental Exposure
Are environmental agents robbing us of both life span and life
expectancy, or are we approaching natural maximums of both?
Should we concentrate our research effort less on the study of aging
processes and more on living longer in the midst of the noxious
substances in our environment? Should we devote more effort to
the study of environmental induction of age-associated disease?
By eliminating the causes of age-associated disease that are not
inherently related to the aging processes, we can probably increase
the quality of life in old age. If mechanisms of development of
disease depend more on basic underlying processes of aging than on
factors that can be eliminated from such processes, the piecemeal
study of the diseases of old age will have only limited success.
Our inability to separate the aging processes from environmental
influences lies at the heart of the problem.
Precisely how environmental agents affect aging processes is
not known. The subject has not been adequately studied, and
aging processes themselves have not been adequately described.
However, it is reasonable to assume that environmental agents
acting at critical periods of development can affect age-related
phenomena later in life.
For example, exposure to an agent that affects or interferes
10
OCR for page 11
AGING AND ENVIRONMENTAL EXPOSURE
11
with the development of stem celb during the fetal stage, in in-
fancy, or in early childhood might contribute to nervous system
decline in later life. For instance, a depletion of precursors of the
neurons of the substantia nigra might increase the probability of a
comparatively early onset of Parkinson's disease. A change in the
susceptibility to a great many other pathophysiologic accompani-
ments of aging might have, in part, such an etiology. In addition,
the elderly might be particularly vulnerable to the effects of many
environmental agents because of normal age-related alterations in
cellular structure and function and a general decrease in the abil-
ity to maintain physiologic homeost~is, or because of alterations
acquired as a result of environmental exposure.
The classic studies of Nathan Shock (1977) suggest that there
are almost linear declines in the functional capacity of many (if
not all) physiologic systems in many but not all humans after age
30. The rate of decline varies among organ systems, from 2.5~o per
decade in basal metabolic rate and nerve conduction velocity to
logo per decade in renal and respiratory capacity. It follows that
the homeostatic reserve of the organism, which is proportional
to the dynamic range of the integrated functions of physiologic
systems, declines with age.
Clinical studies have revealed that a number of adaptive re-
sponses are diminished in old people. For example, body tem-
perature is influenced by increases in ambient temperature to a
far greater extent in the old adult than in the young adult. This
phenomenon is attributable largely to the slower onset of vasodi-
latation and sweating that follows an increase in ambient temper-
ature. Homeostatic responses are also blunted after an increase in
blood glucose concentration, blood pressure, or heart rate.
Young adults are protected from environmental stresses by
their homeostatic reserves. Their deaths more often result from
injuries or diseases that exceed their homeostatic capacity. Over
95~o of deaths in young adults can be associated with a pathologic
state. However, in one study of deaths among people who were
more than 85 years old, 26~o of the subjects had "no acceptable
cause of deaths (Kohn, 1982~. They might have died of environ-
mental stresses that would have caused no mortal complications
in young people.
Epidemiologic studies have shown that older patients admitted
to hospitals are slower to return to good health: the duration of
hospitalization and its associated mortality increase between the
OCR for page 12
12
AGING IN TODAY'S ENVIRONMENT
ages of 35 and 75 years. Bed rest itself can so Recondition an older
person that the simple act of dressing after 2 weeks in bed can
induce maximal heart rate in an 8~year-old.
BASIS O1? THE SCIENTIFIC PROBLEM
The scientific problem of distinguishing states of disease and
impaired function that result only from an essential underlying
process- aging from states that are caused by environmental
exposures is complicatedly by the fact that aging and chronic envi-
ronmental exposure are absolute concorn~tants. Even in the labm
ratory, environmental influences can be only minimized, not elim-
inated. The effects of diet and other essential components of the
laboratory environment can be successfully reproduced and oh~-
served as changes in structure, function, and disease states in
inbred laboratory animals.
However, the extent to which the characteristics of d~eterio-
ration seen in animals that age in a controlled environment are
predictive for anunals of the same species that age in another
environment is limited, as is extrapolation to different animals
whether they age in similar or dissimilar environments. Further-
more, the specific effects of intrinsic aging—those produced solely
by an essential, constitutive biologic process that would~ occur in
an optimal and absolutely nonperturbing environment have not
been identified.
Gerontologists and toxicologists have assumed that interac-
tions between aging and the laboratory environment constitute
a process that can be accounted for in a "control" population.
However, both groups have sought descriptors of structure, func-
tion, or disease that are relevant only for independent underlying
~ ~ The two groups have
termed these descriptors "biomarkers of agings and ~biomarkers
of toxicity, respectively. Much effort is being expended in the
search for biomarkers that best predict aging or their. r"~:nnn.c:" in
an organism, but to date then- Art.. Hart Up mailer r~or+;=ll~r
successful.
-
processes ot e~ther aging or toxic stress.
.
~ ~ __= ~ ~ _^A— -_ ^~^
~ ~ ~~} e~A Us
The failure to identify biomarkers as descriptors exclusively
of aging or of toxicity might simply reflect our meager knowledge
of the essential mechanisms that underlie these processes. Or it
might reflect a basic interplay between aging and environment
through homeostatic and compensatory mechanisms that make
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AGING AND ENVIRONMENTAL EXPOSURE
13
unlikely the identification of universal and exclusive biomarkers of
aging or of a specific toxic process. If toxic agents are administered
for short periods at high concentrations or if aging occurs in an
artificially pristine environment, the two processes- might become;
more clearly separable. But the separation is extremely difficult
to discern in experiments relevant to human beings, who age for
extended periods in environments that contain multiple agents at
various concentrations.
The difficulty of applying the results of experiments on ag-
ing in laboratory animals to human beings is also related to
extrapolation across wide dose ranges, from laboratory to real
environment, and from laboratory animal to human being. Va-
lidity depends on various biologic assumptions, for example, as
to the shape of the dose-response curve, the interactions among
many agents, and the biologic similarity of the laboratory animal
to the human being. In the case of aging in a multiagent toxic
environment, such assumptions are difficult to propose in exact
terms or, once proposed, to defend rigorously.
These problems complicate not only laboratory study of aging
in a toxic environment, but also epidemiologic and demographic
studies of the aging of human populations in various environments.
The latter kinds of study are also confounded by our inability
to distinguish between the contribution of intrinsic aging to the
health status of the aged and the contribution of environmental
factors. That inability confounds the determination of the type of
old age we should expect in terms of life expectancy and disease
prevalence.
STRUCTURE OF TEE REPORT
This report describes current knowledge about the relation-
ship between chemicals and aging from two perspectives: the ef-
fects of chemicals on the aging processes and the effects of aging on
the body's ability to respond to environmental chemicals. It dis-
cusses some specific needs for research in aging and toxicology, sug-
gests the need for a data base on ~gerontotoxicology," and guides
the development of such a data base. In separate chapters, it de-
fines and describes the aged population (Chapter 2), reviews basic
principles of gerontology and toxicology to identify relationships
between aging processes and environmental exposures (Chapters
3 and 4), identifies candidate situations for environmental effects
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14
on aging processes (debater 5)) examines potable ~tuatlons far
averse environment impacts on the elderly (Chapter 0~$ out-
Une~ boa the use of model system can expand the knowledge
bee in both toxicology ad gerontology (abater 7~, and presents
the committee conclusions and reco~end~t~ns (Chapters 8
ad g).
Representative terms from entire chapter:
environmental exposure
