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AGING
In Today's Environment
Committee on
Chemical Toxicity and Aging
Board on Environmental Studies and Toxicology
it_ . . ~ . ,- . - .
commission on . Ate Sciences
National Research Council
NATIONAL ACADEMY PRESS
Washington, D.C. 1987
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NOTICE: The project that is the subject of this report was approved by the Governing
Board of the National Research Council, whose members are drawn from the councils
of the National Academy of Sciences, the National Academy of Engineering, and the
Institute of Medicine. The members of the committee responsible for the report were
chosen for their special competences and with regard for appropriate balance.
This report has been reviewed by a group other than the authors according to
procedures approved by a Report Review Committee consisting of members of the
National Academy of Sciences, the National Academy of Engineering, and the Institute
of Medicine.
The National Academy of Sciences is a private, nonprofit, self-perpetuating society
of distinguished scholars engaged in scientific and engineering research, dedicated to the
furtherance of science and technology and to their use for the general welfare. Upon
the authority of the charter granted to it by the Congress in 1863, the Academy has
a mandate that requires it to advise the federal government on scientific and technical
matters. Dr. Frank Press is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter
of the National Academy of Sciences, as a parallel organization of outstanding engineers.
It is autonomous in its administration and in the selection of its members, sharing with
the National Academy of Sciences the responsibility for advising the federal government.
The National Academy of Engineering also sponsors engineering programs aimed at
meeting national needs, encourages education and research, and recognizes the superior
achievements of engineers. Dr. Robert M. White is president of the National Academy
of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of
Sciences to secure the services of eminent members of appropriate professions in the
examination of policy matters pertaining to the health of the public. The Institute acts
under the reponsibility given to the National Academy of Sciences by its congressional
charter to be an adviser to the federal government and, upon its own initiative, to
identify issues of medical care, research, and education. Dr. Samuel O. Thier is president
of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences
in 1916 to associate the broad community of science and technology with the Academy's
purposes of furthering knowledge and advising the federal government. Functioning in
accordance with general policies determined by the Academy, the Council has become the
principal operating agency of both the National Academy of Sciences and the National
Academy of Engineering in providing services to the government, the public, and the
scientific and engineering communities. The Council is administered jointly by both
Academies and the Institute of Medicine. Dr. Frank Prep and Dr. Robert M. White are
chairman and vice-chairman, respectively, of the National Research Council.
This study was prepared under Grant No. CR-812961-01-0. The content of this
publication does not necessarily reflect the views or policies of the U.S. Environmental
Protection Agency or the U.S. Department of Health and Human Services, and an official
endorsement should not be inferred.
Available from:
Committee on Chemical Toxicity and Aging
National Research Council
2101 Constitution Avenue, N.W
Washington, DC 20418
Printed in the United States of America
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COMMITT1:E: ON CHEMICAL TOXICITY AND AGING
ROBERT N. BUTLER, Department of Geriatrics and Adult
Development, Mt. Sinai Medical Center, New York,
New York, Co-Chairman
EMIL A. PFITZER, Department of Toxicology and Pathology,
Hoffmann-La Roche Inc., Nutley, New Jersey, Co-Chairman
PATRICIA BUFFLER, Epidemiology Research Unit, University
of Texas Health Science Center, School of Public Health,
Houston, Texas
FREDERICK DE SERRES, Research Triangle Institute,
Research Triangle Park, North Carolina
BARBARA GILCHREST, Department of Dermatology, Boston
University Hospital, Boston, Massachussetts
RONALD HART, National Center for Toxicological Research,
Jefferson, Arkansas
THOMAS JOHNSON, Department of Molecular Biology and
Biochemistry, University of California, Irvine, California
CARL KUPFER, National Eye Institute, Bethesda, Maryland
GEORGE MARTIN, Department of Pathology, University of
Washington, Seattle
EDWARD MASORO, Department of Physiology, University of
Texas Health Sciences Center, San Antonio, Texas
DAVID PRESCOTT, Department of Cellular and Developmental
Biology, University of Colorado, Boulder
PETER SPENCER, Institute of Neurotoxicity, Albert Einstein
College of Medicine, New York, New York
ELIOT VESELL, Department of Pharmacology, Hershey
Medical Center, Pennsylvania State University, Hershey,
Pennsylvania
ROBERT VESTAI,, Veterans Administration Medical Center
Boise, Idaho
MARK WEKSLER, Division of Geriatrics and Gerontology,
Cornell University Medical College, New York, New York
JERRY WILLIAMS, Johns Hopkins University Medical Center
Baltimore, Maryland
· ·—
111
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Natlon~ Resewn Call Stag
ANDREW a. POPE, Pant D~-
JEANN~ RICHARDS, Research Assistant
NORMAN G-SSBL^~ Edna
O~ COLDSBO-) Pant Sag
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BOARD ON ENVIRONMENTAL STUDIES AND
TOXICOLOGY
DONALD F. HORNIG, School of Public Health, Harvard
University, Boston, Massachusetts, Chairman
ALVIN L. ALM, Alliance Technologies Corporation, Bedford,
Massachussetts
RICHARD N. L. ANDREWS, UNC Institute for Environmental
Studies, University of North Carolina, Chapel Hill, North
Carolina
DAVID BATES, Department of Medicine, UBC Health Science
Center Hospital, Vancouver, B.C.
RICHARD A. CONWAY, Engineering Department, Union
Carbide Corporation, South Charleston, West Virginia
WILLIAM E. COOPER, Department of Zoology, Michigan State
University, East Lansing, Michigan
BENJAMIN G. FERRIS, Department of Environmental Science
and Physiology, Harvard School of Public Health, Boston,
Ma~a~chussetts
SHELDON K. FRIEDLANDER, Department of Chemical
Engineering, University of California, Los Angeles, California
BERNARD GOLDSTEIN, Department of Environrr~ental and
Community Medicine, UMDN]- Robert Wood Johnson
Medical School, Piscataway, New Jersey
DONALD MATTISON, Department of Obstetrics and
Gynecology, University of Arkansas for Medical Sciences,
Little Rock, Arkansas
PHILIP A. PALMER, Engineering Department, E.~. DuPont de
Nemours & Co., Wilmington, Delaware
DUNCAN T. PATTEN, Center for Environmental Studies,
Arizona State University, Tempe, Arizona
EMIL PFITZER, Department of Toxicology and Pathology,
Ho~mann-I`a Roche Inc., Nutley, New Jersey
PAUL PORTNEY, Resources for the Future, Washington, D.C.
PAUL RISSER, University of New Mexico, Alberquerque, New
Mexico
WILLIAM H. RODGERS, School of Law, University of
Washington, Seattle, Washington
F. SHERWOOD ROWLAND, Department of Chemistry,
University of California, Irvine, California
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LIANE B. RUSSELL, Biology Division, Oak Ridge National
Laboratory, Oak Ridge, Tennessee
ELLEN SILBERGELD, Toxics Program, Environmental Defense
Fund, Washington, D.C.
GLENN I. SIPES, Department of Toxicology and Pharmacology,
University of Arizona School of Medicine, Tucson, Arizona
National Research Council Staff
DEVRA DAVIS, Director, BEST
JACQUELINE PRINCE, Staff Associate
V1
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Preface
~ 1985, the Environmental Protection Agency (EPA) and
the National Institute of Environmental Health Sciences (NIEHS)
asked the National Academy of Sciences to evaluate current in-
formation about the effects of environmental chemicals on aging
processes and the aged population and to recommend research
strategies in this area. In response to this request, the National
Research Council's Board on Environmental Studies and Toxicol-
ogy established the Committee on Chemical Toxicity and Aging.
The formation of the committee constituted one of the country's
first organized efforts to bring together experts in the fields of
gerontology and toxicology to consider the interface between the
two scientific disciplines.
For many topics, the government has seen fit over the years
to organize interagency groups to ensure information exchange
and coordination or to speed the implementation of specific steps
to a goal. Examples include the Nutrition Coordinating Com-
rn~ttee, the Biotechnology Coordinating Committee, and groups
concerned with such topics as radiation and regulatory matters.
These groups have a mixed record of effectiveness. Often they
are created by one administration but then fall into disuse and
disappear with the next. Still, for those subject areas that are
of interest and concern to many different agencies and that can
· ~
V.11
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benefit from a forum for discussion and coordination, the idea of
forming such a committee Is attractive.
Aging is such an area. The responsibility for research and
policy formation for aging ~ found in several agencies: The major
focus of basic research and training is at the National Institute
on Aging (which includes the Interagency Committee on Aging
Research), a major clinical training function is carried out by the
Veterans' Adm~n~tration, and there are several policy eoord~nat-
ing groups at the level of the Assistant Secretary for Health at
the Department of Health and Human Services. Although it was
beyond the scope of this committee's task to evaluate government
programs on aging, the need was apparent to this committee for an
increased effort in coordinating and conducting research on aging
that would include toxicology.
This report, which is the result of the committee's delibera-
tions, reviews the important environmental factors that influence
the aging processes and the aged, and it recommends research that
needs to be done to improve our understanding of aging in today's
environment and the health and weD-being of the aged population.
On behalf of the committee, we would like to express our am
preciation to the National Research Council staff and others who
facilitated this committee's deliberations and work in preparing
this document. We specifically thank Andrew Pope for his skill-
ful writing, editing, and facilitation of committee process, Jeanne
Richards for her enthusiastic contributions in literature research
and drafting of materials, Edna Paulson for her tireless dedication
to accuracy in reference verification, Devra Davis for her valuable
guidance and creative oversight, Alvin Lazen for his sound direc-
tion and sage advice, and Norman Grossblatt for his professional
judgment and logic in editing the report.
We are also grateful to the sponsors, EPA and NIEHS, and
to the project officers from those agencies: Scott Baker for his vi-
sionary planning, initiation, and continued support of this project,
and Linda Birnbaum for her enthusiastic technical guidance and
assistance.
Robert N. Butler
Emil A. Pfitzer
Chairmen
· - ~
van
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Contents
EXECUTIVE SUMMARY
1 AGING AND ENVIRONMENTAL EXPOSURE.
Basis of the Scientific Problem, 12
Structure of the Report, 13
2 THE AGING POPULATION AND THE
PSYCHOSOCIAL IMPLICATIONS OF AGING 15
Demographic Considerations of an Aging Population, 15
Psychosocial Environment, 26
3 PRINCIPLES OF GERONTOLOGY
Conceptual Context of Gerontology, 28
Theories of Aging, 32
Deterministic Theories, 33
Stochastic Theories, 33
Biomarkers of Age or Aging, 39
Altered Susceptibility of the Aged, 42
4 PRINCIPLES OF TOXICOLOGY IN THE
CONTEXT OF AGING 46
Chemical Fate and Effect, 49
Absorption, 51
Distribution, 52
......... 10
28
L'C
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Metabolism and Elimination, 53
Mechanisms of Toxicity at the Molecular, Cellular, and Tissue
Level, 58
Molecular Action, 59
Cellular Effects, 60
Effects at the Tissue Level, 61
Pharmacogenetics, 61
Biologic Markers, 67
Toxicity Testing, 69
5 CHARACTERISTICS OF THE ENVIRONMENT,
AGING, AND THE AGED ~ 72
Nutrition, 75
Effects of Nutrition on Toxicity, 76
Nutrition and Cancer, 78
Nutrition and Aging, 80
Special Dietary Requirements of the Aged, 90
Pharmaceuticals, 94
Demographic Considerations, 94
Patterns of Drug Use and Drug Prescribing, 95
Medication Compliance in the Elderly, 98
Adverse Drug Reactions, 99
Life-Style, 101
Deliberate Chemical Exposure, 101
Learned Helplessness, 102
Atrophy of Disuse, 102
Indoor Pollutants, 103
6 ENVIRONMENTAL EFFECTS ON AG~ASSOCLATED
DISEASES AND CHANGES IN ORGAN FUNCTION ..109
Demographics of Age-Associated Diseases, 110
Skin, 121
Vision, 124
Cataracts, 124
Glaucoma, 126
Diabetic Retinopathy, 127
Aging-Related Macular Degeneration, 127
Hearing, 128
Nervous System, 128
Changes Associated with Aging, 128
Induced Disorders and Diseases, 130
Neurotoxicants, 131
x
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Respiratory System, 135
Cardiovascular System, 136
Renal System, 139
Immune System, 140
Sexuality, 142
Role of Environment in Bone Metabolism and Vitamin D
Nutrition, 143
7 MODEL SYSTEMS FOR THE EVALUATION OF
TOXIC AGENTS AFFECTING AGING OR
AG~RELATED DISEASES 145
Considerations In Choosing and Designing Mode}
Systems, 146
Examples of Model Systems, 149
In Vitro Modem, 149
Nonmammalian Animal Models, 152
Mammalian Models, 156
Epidemiologic Models, 159
Life-Span Modulation by Drug Treatment, 160
8 CONCLUSIONS
9 RECOMMENDATIONS.
Research, 165
Education, 168
Funtling and Resources, 169
REFERENCES -
162
.165
171
APPENDIX: Resources for Studying Aging 209
COMMITTEE BIOGRAPHIES ...............................
X1
213
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Tables and Figures
TABLES
Table 2-1 Dependence of Civilian Noninstitutionalized Popula-
tion in Activities of Daily Living, United States, 1979,
24
Table 2-2 Dependence of Nurs~ng-Home Residents in Activities
of Daily Living, United States, 1977, 24
Table 2-3 Life Expectancy at Birth for Females and Males in
Selected Countries, 25
Table (1 Monogenic Metabolic Pharmacogenetic Conditions and
Putative Aberrant Enzymes, 65
Table ~1 Action of Food Restriction on Age-Associated Physio-
logic Changes, 83
Table ~2 Action of Food Restriction on Age-Associated Disease
Processes, 84
Table 6-1 Examples of Age-Associated Changes in Organ Struc-
ture and Function and Possible Related Agents, Medi-
cal Conditions, or I,ife-Styles, 110
Table 6-2 Death Rates for the 10 I,eading Causes of Death for
Ages 65 and Over, by Age, 1976, 119
Table 6-3 Prevalence of Selected Impairments by Age and Sex,
United States, 1981, 120
X11
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FIGURES
Figure 2-1 Life expectancy at birth by race and sex, United States,
195~1983, 17
Figure 2-2 Death rates by age and sex, United States, 195~1984,
18
Figure 2-3 Average expectation of life at specified ages in selected
years, l9C~L1982,19
Figure 2-4 Percent of cohort of white females surviving to specific
ages, according to current life tables for United States,
198CL2050,20
Figure 2-5 Percentage increase in older population, by decade,
190~2050, 22
Figure 2-6 Percentage of population with severe activity limita-
tion, 1982, 25
Figure 3-1 Estimates of cros~sectional versus longitudinal difl3er-
ences with age in performance on a test of cognitive
function (the verbal meaning test) by human subjects
of various ages, 32
Figure 4-1 Schematic depiction of established or suspected envi-
ronmental factors that can alter genetically controlled
rates of drug elimination, 63
Figure ~1 Ag - specific incidence rates for female breast cancer in
four population groups, 111
Figure ~2 Ag~adjusted death rates for persons 65 years of age
and over, according to leading causes of death: United
States, 195CL1979, 113
Figure ~3 Age-adjusted death rates for persons 65 years of age
and over, according to sex: United States, 194~1978,
114
Figure 6-4 Age-adjusted cancer death rates for selected sites,
males: United States, 193~1978, 115
Figure ~5 Age-adjusted cancer death rates for selected sites, fe-
m~es: United States, 193C~1978, 116
Figure ~6 Major cardiovascular diseases: age-specific mortality
rates versus all causes of mortality, 117
Figure ~7 All sites: age-specific cancer incidence and mortality
rates versus all causes of mortality, 118
·..
}C111
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