NIH 1998 Almanac/The Organization/NIA/
National Institute on Aging : Research Programs
Intramural Research
The bulk of the NIA intramural research program is conducted at the Gerontology
Research Center in Baltimore, Md.
The Laboratory of Neurosciences operates a research program from the Clinical
Center at NIH. Via the NIH medical staff fellow, staff fellowship, a cooperative geriatric
medicine fellowship with Johns Hopkins, intramural research training awards, and visiting
programs, scientists at various stages of their careers gain sophisticated gerontology
experience at the center. Over 300 postdoctoral investigators have been trained at the GRC
since 1940.
The Laboratory of Clinical Investigation (LCI) conducts research on the effects
of aging on human physiology with emphasis on factors leading to age-related disease such
as diabetes, osteoporosis, osteoarthritis, Alzheimer’s disease, and prostate cancer
as well as general musculoskeletal frailty. The laboratory consists of several sections.
The longitudinal studies section manages and operates the Baltimore Longitudinal Study
of Aging (BLSA), which, for the past 40 years, has collected data and biological samples
from adult volunteers of all ages who are studied intensively at regular intervals. To
date, nearly 2,500 men and women have particpated.
The current BLSA population consists of 571 men and 546 women of whom 14 percent are
members of an ethnic minority.
The BLSA historical database and sample repository provide unique resources for testing
a wide variety of hypotheses regarding the physiology of aging and the antecendents of
age-related disease.
In addition, ongoing longitudinal and cross-sectional investigations involving BLSA
participants are conducted by individual NIA scientists throughout institute laboratories.
Examples of these efforts include studies of cardiovascular function as it relates to
arterial compliance and responsivity, the predictive value of prostate specific antigen
and other circulating factors for prostate cancer risk, the effects of aging on neural
activity as determined by functional MRI scanning of the brain, and a study of women 45-55
years of age documenting the changes in hormonal bone metabolism, body compositional, and
cardiac risk factors during menopausal transition. The most promising information obtained
from observational studies in the BLSA are used to help plan and implement basic
laboratory studies and clinical intervention studies aimed at better understanding
mechanisms of aging and ameliorating or preventing age-related illness or frailty.
Scientists in other LCI sections are engaged in experimental studies to improve the
understanding of mechanisms leading to type 2 (adult onset) diabetes and in the search for
better and more effective therapies for controlling blood sugar in diabetics; in a large
clinical intervention trial testing effects of replacement with growth hormone and/or
gender appropriate sex steroid hormones in older men and women on musculoskeletal and
cardiovascular function; and in efforts to understand the relationships among glucose
metabolism, obesity, hypertension, diabetes, and cardiovascular risk factors in the
elderly.
The Laboratory of Personality and Cognition (LPC) conducts research on
individual differences in psychosocial and intellectual functioning with aging and their
influence on health and adaptation. LPC researchers are actively engaged in dispelling
myths on aging, personality, and health, and have contributed new insights about the
stresses faced by aging adults, the methods and strategies used by them to cope, and the
effectiveness of their coping efforts. The LPC also conducts research on early markers of
Alzheimer’s disease as well as cognitive performance and aging, emphasizing the
psychological mechanisms underlying age-related changes in memory, learning, and
reasoning.
Researchers in the Laboratory of Cellular and Molecular Biology conduct studies
at the cellular and molecular levels to assess basic mechanisms of aging that affect
physiologic function. Included are studies on signal transduction, structural biology,
stress responses, gene expression, oxygen radicals and mechanisms of neurodegeneration.
Manipulations, such as diet, exercise, pharmacological/endocrinological and genetic
interventions, are examined.
Research in the Laboratory of Biological Chemistry focuses on molecular and
cellular responses to extracellular signals and encompasses studies on signal transduction
pathways regulating the cellular response to stress and proliferative stimuli, cell cycle
control, and mechanisms of carcinogenesis. Particular emphasis is placed on understanding
the factors (e.g., induced gene products) that determine cell fate following treatment of
cells with growth stimulating or toxic agents and exploring the basis for age-related
alterations in responsiveness to certain stimuli.
Studies employ a variety of model systems including neuronal cells, T cells, and
primary hepatocytes. In addition, scientists are studying several tumor supressor genes
for their roles in regulating growth and investigating gene mutations involved in the
development of human ovarian cancer.
The Laboratory of Genetics, which opens in the fall of 1998, studies genes
involved in the overall process of aging as well as in aging-related diseases and
conditions such as type 2 diabetes and premature ovarian failure. Also studied is how the
rate of aging or regeneration of specific tissues depends on genes that are often
critically involved in development, genetics and regulation of selected embryonic
processes. A program in the laboratory focuses on mitochondria functions and their change
with aging. Another program investigates the mechanism of somatic hypermutation.
The Laboratory of Molecular Genetics (LMG) is investigating the molecular basis
for aging and age-dependent diseases, notably cancer. Studies are focused on DNA- related
mechanisms such as genomic instability, DNA repair, DNA replication and transcription. The
increased levels of DNA damage that have been observed with aging may be due to changes in
DNA repair. A special interest is in the fine structure of DNA repair and the DNA repair
processes in individual genes. Molecular mechanisms are being investigated and changes in
the mechanisms with aging are studied.
The overall goals of the Laboratory of Cardiovascular Science are 1) to identify
age-associated changes that occur within the cardiovascular system and to determine the
mechanisms for these changes; 2) to study myocardial structure and function and to
determine how age interacts with chronic disease states to alter function; 3) to study
basic mechanisms in excitation-contraction coupling and how these are modulated by surface
receptor signaling pathways in cardiac muscle; 4) to determine the chemical nature and
sequence of intermediate reactions controlling movement of ions through ionic channels and
pumps in myocardium; 5) to determine behavioral aspects of hypertension; 6) to determine
normal and abnormal function of vascular smooth muscle and endothelial cells; and 7) to
establish potentials and limitations of new therapies such as gene transfer.
In meeting these objectives, studies are performed in human volunteers, intact animals,
isolated heart and vascular tissues, isolated cardiac and vascular cells, and subcellular
organelles.
Laboratory of Immunology (LI) investigators study the biological, biochemical,
and molecular mechanisms of inflammation and cellular activation in normal and aged
leukocytes. The program area encourages basic research on the regulation of cellular
migration; cancer biology; the regulation of and signaling through growth factor receptors
on leukocytes; and the various immuno-deficiences of aging and AIDS. Additional studies
within LI involve examining the relationship between telomere length and telomerase
expression during the aging process. Within another section of the laboratory, several
researchers are examining B lymphocyte development and maturation using various
genetically altered and aged animal models.
Investigators in the Laboratory of Neurosciences study the function and
structure of the central nervous system in relation to neurodegenerative and developmental
disorders. Basic studies involve brain phospholipid metabolism during neuroplas-ticity and
functional activation, and blood-brain barrier transport and drug delivery.
Studies in the cerebral metabolism section deal with research on animal models related
to human aging and disease. Previously, physicians, pharmacologists, and physiologists
have worked on clinical brain imaging studies using positron emission tomography and
magnetic resonance. Studies have demonstrated that early metabolic deficits can be
detected in brains of participants with a single memory disorder, presaging the later
development of Alzheimer’s dementia. Simulation PET studies have shown that metabolic
deficits in Alzheimer’s disease can be partially reversed with appropriate cognitive
tests.
Epidemiology, Demography, and Biometry Program
This program collects and evaluates data on health and illness in the older population.
The intramural scientific research carried out by EDBP staff is supplemented by research
contracts, interagency agreements, and numerous working arrangements with Federal and
non-Federal organizations. Basic information is generated on current and projected health,
and social status of older people.
A multicenter, prospective study of 14,000 older Americans entitled "Established
Populations for Epidemiologic Studies of the Elderly" (EPESE) was initiated in 1980
to prospectively evaluate social, behavioral and environmental factors related to
morbidity and mortality. A public use version of the EPESE baseline dataset for all four
sites, as well as followup data from the sites, was made available to investigators in the
U.S. The EPESE serves as a primary resource for a broad variety of epidemiologic studies
of the elderly, including minorities.
The Women’s Health and Aging Study, launched in 1991, is a comprehensive study of
functional decline in older women with moderate to severe disability. The multiyear
effort, being conducted under a contract awarded to Johns Hopkins University School of
Medicine, will closely follow about 1,000 women to evaluate changes in physical status
over a 3-year period. Other factors, such as mortality and use of long-term care, are
being evaluated.
In 1991 the EDBP started the Honolulu-Asia Aging Study. A complex cross- national study, research focuses on people already participating in the Honolulu Heart
Program, an ongoing prospective study of cardiovascular diseases of American men ages 70
to 90 of Japanese ancestry. The aging study has use of the heart program participants as a
resource for research on dementia and to compare results with those generated by parallel
studies in other Asian-ancestry populations. Research has shown important differences
between the Japanese ancestry living in Hawaii and in Japan. These studies provide clues
as to the genetic and lifestyle components.
The Veterans Study of Memory in Aging was initiated in 1994 with Duke University. The
project has recruited 3,000 U.S. Navy veterans who served 1944-45. Half of these men
suffered closed head injury with loss of consciousness in 1944-45 and possibly at other
times in their lives; the other half suffered no such head injury. Based upon cognitive
screening, researchers will retrospectively study the association between head trauma with
Alzheimer’s disease and other degenerative dementias.
Progressive loss of muscle mass, or sarcopenia, has been hypothesized to be a common
pathway by which multiple diseases contribute to disability. EDBP initiated the
"Dynamics of Health and Body Change" (HEALTH ABC) study to characterize the
extent of loss of muscle mass in older men and women, identify clinical conditions
accelerating the loss of muscle, and examine the health impact of loss of muscle on
strength, endurance, disability, and diseases common in old age. Approximately 3,000 men
and women, ages 70-79, about half of whom are African American, are followed for 7 years
for new onset of physical disability. The HEALTH ABC will provide invaluable information
on optimal timing for interventions to prevent or reverse muscle loss and on high-risk
groups most likely to benefit.
The EDB program supported the collection and analysis of data on cause of death and
characteristics of the last year of life in the 1993 National Mortality Followback Survey
(NMFS) conducted by NCHS, CDC. This survey supplements information from death certificates
in the vital statistics file with information on characteristics of the decedent featuring
an over sampling of centenarian decedents. Agreements are in place with the SSA and HCFA
to link the NMFS data with administrative records from those two agencies. Analytic plans
call for a joint effort in the production of a report on life and death amongst the oldest
of the old.
Other areas of interest include disability and physical function; hip fracture and
osteoporosis; heart disease; dementia; sleep disturbance; hearing and vision disorders;
methodologic issues in aging research; and cross-cultural and international studies of
aging and the diseases of aging.
Biology of Aging Program
The program supports biomedical studies through various NIH grant mechanisms and
contracts. The program plans, implements, and supports fundamental molecular, cellular and
genetic research on the mechanisms of aging. It also supports resource facilities that
provide aged animals and cell cultures for use in aging research.
Animal Models. This program area funds research on the identification and
development of animal models, both mammalian and lower organism, for use in aging
research.
Biomarkers. This area supports research to identify and validate a panel of
biomarkers of aging in a rodent model, with eventual application of these biomarkers to
humans.
Cell Biology. This program area investigates aging at the cellular level and
includes membranes and membrane receptors, growth factors, signal transduction,
extracellular matrix, skin and cartilage, intercellular communication, and proteoglycan
structure and function.
Differentiation. This area supports research on muscle biology and muscle
regeneration, developmental genetics related to aging, and age-dependent loss of
differentiated cell function.
Endocrinology. The endocrinology program area supports basic research aimed at
understanding the age-related changes in hormone production, metabolism, and action;
reproductive aging; biology of menopause; age-related changes in control of prostate
growth; and age-related changes in hormonal regulation of bone growth and bone cell
function.
Genetics. This area supports research aimed at longevity assurance genes,
evolutionary genetics of aging and longevity, sex-dependent biological influences on
aging, and the role of somatic cell mutations in aging.
Immunology. This program area encourages research on age-related changes in the
immune system including regulation of lymphocyte proliferation, regulation of immune
specificity, response of the immune system to biochemical stimuli, autoimmune disease and
other immunopathology, endocrine and neuroendocrine control of immune function, and
interventions to retard and/or correct age-related decline in immune function.
Molecular Biology. This area funds studies on the generation and metabolism of
free radicals, repair of free radical damage in DNA and lipids, mechanisms of programmed
cell death, and interventions to extend life span of model organisms.
Molecular Genetics. This area supports research on regulation of cell proliferation
in normal, aging, and transformed cells; senescence-related changes in cell
cycle-dependent gene expression, the role of telomeres in cell senescence; and age-related
changes in gene expression.
Nutrition and Metabolism. This program supports research on nutritional factors in
age-related disease, changes in RDAs with age, roles of nutrition in immune function,
roles of dietary factors in oxidative damage and antioxidant defenses, the role of
nutrition in age-related changes in tissue function, and the age-related changes in the
metabolism of nutrients.
Pathobiology. This area supports research on the molecular basis of Werner's
syndrome, arthritis, cardiovascular and other age-related diseases; age-related changes in
mitochondrial function, molecular basis of age-related pathology; and age-related changes
in response to biological stress, especially heat shock and acute phage responses.
Physiology. This area supports research on age-related changes in osteoblast and
osteo-clast function and bone matrix and electrolyte balance.
Protein Structure and Function. This area supports research on protein oxidation
and turnover of damaged proteins, protein tertiary structure, glycation of proteins and
the metabolism of glycated proteins, and the post-translational modification of proteins.
The Biology of Aging Program also includes the Office of Biological Resources and
Resource Development and the Office of Nutrition. These offices coordinate NIA activities
in the indicated areas and serve as liaison between NIA and other agencies.
Geriatrics Program
The program supports the development of clinical research on the special medical needs
and problems of the growing aging population in the U.S.
The cardiovascular/pulmonary/renal program area develops and supports research on
problems such as alterations in blood pressure regulation with age; isolated systolic
hypertension; orthostatic hypotension; aging changes in microcirculation; age-associated
alterations in the composition of arteries and the effect of these alterations on
cardiovascular function; age-related changes in quality, quantity, and function of the
myocardium and conduction system of the heart; and changes with age in kidney and
pulmonary function.
The centers program includes the support of the Claude Pepper Older American
Independence Centers.
The endocrinology program area encourages and supports research aimed at providing an
understanding of the age-related changes in endocrine function, including menopause, the
mechanisms underlying these changes, and the impact of these changes on other physiologic
systems.
The geriatric research and training program area supports clinical research on
disorders that are concentrated predominately among older people or that are associated
with increased morbidity and mortality in the elderly. In addition to these specific
clinical problems, the program also addresses the lack of research on clinical problems in
nursing homes and other sites of long-term care for the elderly. Another mission is to
attract new investigators to the field of aging and to further the development of active
investigators in clinical medicine and biomedical research.
The infectious diseases program area supports research on the relationship of
physiologic changes associated with age or chronic disease to susceptibility to
infections.
Other priorities include new strategies for evaluating vaccine efficacy in the elderly,
potential prophylactic techniques for infections in the elderly, age-related changes in
the effects of stresses such as chemotherapy, radiotherapy, and infection on
granulopoiesis and lymphopoiesis, age-related changes in circulating levels of amyloid
proteins and effects of amyloid deposition, and the interaction of aging and processes of
carcinogenesis.
The mission of the musculoskeletal program area is to develop and support basic and
clinical research on age-related changes in function of bone, muscle and cartilage. The
program supports research on risk factors, prevention and treatment of falls, gait
disorders and hip fractures in the elderly, as well as research on osteoarthritis, and
urinary incontinence.
The nutrition, gastroenterology, and metabolism program area develops and supports
basic and clinical research on effects of nutritional factors throughout the life span.
These research goals include age-associated morbidity assessment of nutritional status in
the elderly; effects of aging on nutrient digestion, absorption, and utilization; and the
contribution of nutritional status to the etiology and pathogenesis of diseases prevalent
in the elderly.
The osteoporosis program supports basic and clinical research to identify
age-associated processes which contribute to bone loss and osteoporosis markers and risk
factors that are related to changes in bone mass, bone competence and the predisposition
to falls and strategies based on modifying or reversing these processes. NIA especially
emphasizes research on osteoporosis in advanced age, when the consequences, particularly
those of hip fracture, become more severe and result in escalating morbidity and
mortality.
The Geriatrics Program has begun an area of concentration--the Integration of Aging and
Cancer Research. This aging/cancer interface focuses on age-related changes that
contribute to increased cancer incidence and mortality in older persons; time and its
importance to development of cancer during a person's lifespan; agressive tumor behavior
in the context of the aged host; effects of age and aging on antitumor drugs; and impact
of previous illnesses, disabilities, and degenerative conditions.
Etiologic insights acquired from the development of multiple primary tumors in the
elderly are of special interest. Research on tumors that primarily affect older persons
(e.g., breast, prostate, colon, lung, and non-Hodgkin's lymphoma) are of importance.
Neuroscience and Neuropsychology of Aging
This program fosters and supports extra-mural and collaborative research and training
to further the understanding of neural and behavioral processes associated with the aging
brain. Research on dementias of old age--in particular Alzheimer’s disease--is one of
the highest program priorities.
Neurobiology of Aging. The neurobiology of aging program area fosters research
on age-related cellular and molecular changes in the structure or function of the nervous
system. Studies of neuroimmunology, neurovirology, neuroendocrinology, neuropharmacology,
sensory and motor processes, sleep, biorhythmicity, cell death and neural plasticity are
of particular interest.
Dementias of Aging. The Dementias Branch supports studies of etiology,
pathophysiology, epidemiology, clinical course/natural history, diagnosis and functional
assessment, drug design, drug development and trials, and behavioral managment and
intervention in the dementias and other psychiatric disorders of later life. The branch
emphasizes development of international and multinational investigations.
The basic research section supports research on Alzheimer’s disease and
other age-related neurodegenerative disorders, including identification of genetic loci
associated with inherited forms of these diseases and biochemical and molecular genetic
analysis of the components of amyloid plaques, neurofibrillary tangles, and other abnormal
structures found in the brains of Alzheimer’s disease victims.
The population studies section supports research in the epidemiology of
Alzheimer’s disease and on models for large-area registries for the disorder.
The clinical studies section supports research on the diagnosis, treatment, and
management of patients with Alzheimer’s disease. Research on diagnosis is aimed at
the development and evaluation of reliable and valid multidimensional diagnostic
procedures and instruments.
Research in the treatment and management of Alzheimer’s seeks to develop the
knowledge required to interrupt the course of the disorder, to manage its behavioral
manifestations, and to ultimately prevent it. Treatment approaches include clinical trials
of pharmacologic agents and studies of behavioral and environmental interventions.
Preclinical drug discovery, development, and animal testing studies are important aspects.
The research centers section supports Alz-heimer’s Disease Research Centers and
Alzheimer’s Disease Center Core Grants programs.
Neuropsychology of Aging. The neuro-psychology of aging program emphasizes
research, including the use of animal models, and training on the neural substrate of
age-related changes in basic cognitive processes, learning and memory.
Behavioral and Social Research
This program supports basic social and behavioral research on the aging process and the
problems and needs of older people. It focuses on understanding how psychological and
social aging interact with biological aging processes; how older people relate to social
institutions (e.g., the family, health care systems); and the antecedents and consequences
of the dramatic changes in age composition of the population.
The goal of the program is to produce a scientific knowledge base which--by informing
professional practice, public policy, and everyday life--can maximize people’s
health, effective functioning, independence, and well-being in their middle and later
years. In order to explain the wide diversity among older people, it encourages
comparisons between males and females; persons with differing racial, ethnic, and
socioeconomic background; and inhabitants of countries that vary in styles and standards
of living.
Special attention is given to studies of the oldest old (those age 85 and over), one of
the fastest growing segments of the population. Of special concern is the care of
Alzheimer’s disease patients and their families. Emphasis is also placed on many
kinds of interventions that can prevent, postpone, or reverse such decrements of old age
as chronic ill health, sense of incompetence, memory loss, functional disability, or
withdrawal from active participation in social and economic roles.
Adult psychological development supports research concerned with behavioral and social
mechanisms and processes influencing cognitive and intellectual functioning, personality,
attitudes, and interpersonal relationships over the adult life course. Emphasis is placed
on research relevant to maintaining and improving well-being, independence, and effective
functioning. Research is needed for seeking out the conditions under which age-related
individual changes occur or do not occur, and for supplying information to use in the
design of roles and environments that can utilize the special strengths of middle-age and
older people and that can maintain and enhance their functioning. The two sections
included are: cognitive functioning and aging and personality and social psychological
aging.
Social science research on aging aims to understand the social and environmental
conditions influencing health, well-being, and functioning of people in their middle and
later years. Its three sections focus respectively on the dynamic processes linking
health, behavior, and aging and on those linking social structures with behaviors,
attitudes, health, and status of older people. The sections are concerned with social and
behavioral factors in health and functioning and with assessment and testing of planned
and natural interventions for health promotion/disease prevention.
Special attention is given to research on aging and health care, especially such issues
in long-term care as: family structures and relationships affecting provision of home
care, and interventions to prevent the need for long-term care (e.g., injury prevention
and control). Particular emphasis is placed on studies of long-term care of
Alzheimer’s disease patients and their families in line with the NIA initiative. This
program also encompasses social science research on two other institute-wide initiatives:
gender, health, and longevity, and minority health. The three sections included are:
behavioral geriatrics research, health care organizations, and older people in society.
Demography and population ppidemiology (DPE) supports research and training on the
dynamics and consequences of population aging, and aims to describe and understand the
changing elderly population in terms of its social, demographic, economic, health, and
functional characteristics, and the impact of these changes on society as a whole.
DPE also coordinates policy on aging-related statistical data within the NIA and across
other institutes at NIH as well as with other relevant Federal agencies. The Office on
Demography of Aging is located in the DPE/BSR, the focal point for coordinating
demographic and economic research within NIA. The demography office is also the center of
activity for the Federal forum of aging-related statistics, a group which serves a similar
function in coordinating research government-wide. DPE’s three sections are: health
and retirement economics, demography of aging, and population epidemiology.
