NIH 1999 Almanac/The Organization/NIA/
National Institute on Aging : Research Programs
Resource Centers for Minority Aging Research
In 1998 the NIA launched a new mechanism for enhancing minority research and increasing involvement by minority investigators, an ongoing institute goal. Six facilities have been funded to create Resource Centers for Minority Aging Research (RCMAR). Joining the NIA in funding the centers are the NIH Office of Research on Minority Health and the National Institute of Nursing Research.
The goal of the RCMARs is to close the gap in health, and in the social sequelae of that gap, between minority and nonminority older people. To meet their goals, RCMARs will focus on:
- Mentoring--establishing mechanisms for mentoring investigators who want to study the health of minority elders;
- diversity among minority-health researchers--increasing diversity among researchers who study the health of minority elders;
- recruitment and retention of minority group members for research projects; and
- creating and implementing strategies for projects that will lead to reduced disparity in health status among minority and majority groups.
The bulk of the NIA intramural research program is conducted at the Gerontology Research Center in Baltimore, Md.
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 41 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 623 men and 605 women of whom 14 percent are 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.
Research in the Laboratory of Cellular and Molecular Biology covers a broad range of approaches to assess basic mechanisms of aging that affect physiologic function. Included are studies on structural biology, gene expression, oxidative stress, hematological function, bone metabolism, cartilage, stress responses, nutrition, neuropharmacology, and behavior. Studies employ a variety of models systems including cell culture, rats, mice (including mutants and transgenics), and monkeys.
Technology used includes NMR, NSR, molecular biology, micoarrays, neurochemistry and neuromorphology. One unit is equipped to synthesize pharmaceuticals, including several promising candidates for the treatment of Alzheimer's disease. A major study in the laboratory involves analysis of aging in a longitudinal study of nonhuman primates undergoing caloric modification of their diet.
Research for 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 molecular basis of cancer. 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. Scientists are also studying several tumor supressor genes for their roles in regulating growth and investigating gene mutations involved in the development of human ovarian cancer. Studies employ a variety of in vitro and in vivo model systems including neuronal cells, T cells, and primary hepatocytes and human cancer tissues.
Research in the Laboratory of Genetics is based on the view that aging has genetic determinants as an integrated part of human development. Studies include:
- Transitions between immortal and mortal cells. The transition of immortal embryonic stem cells to mortal differentiating cells is being studied in mice, by differential assays of gene expression in 3.5 days post coitum (dpc) mouse embryos.
- Cohorts of genes involved in the development of selected "nonrenewable" systems. To understand and ultimately try to compensate for loss of cells and tissues during aging, the example of skin appendage is being studied. Studies start from human and mouse hereditary defects in ectodysplasin-A, involved in X-linked ectodermal dysplasia.
- Nuclear organelles that determine large-scale chromatin remodeling events. The transcription remodeling unit is using a combination of approaches to isolate and characterize the critical complexes, including the one that is modified to cause the Werner premature aging syndrome.
- Genes involved in embryonic events that prefigure aging-related phenomena. For example, the human genetics unit is involved in studies of premature ovarian failure, in which the aging phenomenon of early menopause is determined by an increased rate of follicular atresia during fetal life. The laboratory is equipped with state-of-the-art resources for genomic approaches. Among specific technological improvements that are being developed are expression profiling of early developments on microarrays, techniques for the recovery of complete genes in circular, autonomously replicating clones (in the gene recovery unit), and protocols to make and analyze high-quality cDNA libraries from very few cells from subregions of embryos (in the developmental genomics and aging unit).
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
- to identify age-associated changes that occur within the cardiovascular system and to determine the mechanisms for these changes;
- to study myocardial structure and function and to determine how age interacts with chronic disease states to alter function;
- to study basic mechanisms in excitation-contraction coupling and how these are modulated by surface receptor signaling pathways in cardiac muscle;
- to determine the chemical nature and sequence of intermediate reactions controlling movement of ions through ionic channels and pumps in myocardium;
- to determine behavioral aspects of hypertension;
- to determine normal and abnormal function of vascular smooth muscle and endothelial cells; and
- 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.
The Laboratory of Neurosciences (LNS, section on brain physiology and metabolism) conducts its research program at the Clinical Center, NIH, on the Bethesda campus. Investigators study the function and structure of the nervous system in animal models of neurodegenerative and neurodevelopmental disorders and aging, and in postmortem brain tissue from animals and Alzheimer's disease and aged human subjects.
Molecular, neuropharmacological, chemical analytical, modeling and physiological techniques are used in a number of research areas: imaging brain signal transduction in vivo using radiolabeled fatty acid tracers in rodents (with quantitative autoradiography) and humans (with positron emission tomography), quantifying the in vivo dynamics of brain phospholipid metabolism in genetic and induced rodent models of neurotransmitter dysfunction, essential fatty acid deprivation, ischemia, inflammation and action of drugs such as lithium; relating markers of oxidative phosphorylation to markers of synaptic integrity in brain tissue from nonhuman primates and from humans in relation to age and Alzheimer's disease.
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 nonendocrine aspects of bone cell function and bone matrix, renal function and electrolyte balance, prostate growth, uterine function, and erectile dysfunction.
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.
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.
Neuropsychology of Aging
This program fosters and supports extramural 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 management and intervention in the dementias of later life. It also supports the Alzheimer's Disease Centers Program.
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 cognitive decline or Alzheimer's disease. Research on diagnosis is aimed at the development and evaluation of reliable and valid multidimensional procedures and instruments for diagnosis and progression.
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 Alzheimer's Disease Research Centers and Alzheimer's Disease Center Core Grants programs. It also supports the Alzheimer's Disease Data Coordinating Center.
Neuropsychology of Aging. The neuro-psychology of aging program emphasizes research, including the use of animal models, and training on the neural and psychological mechanisms underlying age-related changes in basic cognitive processes, including learning, memory, attention, and language. Studies of age-related changes in emotion also are supported. The use of neural modeling and computational neuroscience approaches to understanding these changes are encouraged.
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 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 epidemiology (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.