|About the Almanac|
|Major NIH Lectures|
In 1974 Congress authorized the establishment of the National Institute on Aging (NIA). The NIA is responsible for "conduct and support of biomedical, social, and behavioral research, training, health information dissemination, and other programs with respect to the aging process and diseases and other special problems and needs of the aged."
December 2, 1971 – The White House Conference on Aging recommends the creation of a separate National Institute on Aging (NIA).
May 31, 1974 – P.L. 93-296 authorizes the NIA and mandates the Institute develop a national comprehensive plan coordinating Department of Health, Education and Welfare agencies involved in aging research.
October 7, 1974 – The National Institute on Aging is established.
April 23, 1975 – The first meeting of the National Advisory Council on Aging is held.
July 1, 1975 – The Adult Development and Aging Branch and Gerontology Research Center becomes the core of the NIA.
December 8, 1976 – The national comprehensive research plan mandated by P.L. 93-296 is sent to Congress.
September 20, 1982 – The NIA Laboratory of Neurosciences Clinical Program admits its first inpatient to a new unit at the NIH Clinical Center.
September 9-11, 1983 – The Institute marks the 25th anniversary of the Baltimore Longitudinal Study of Aging. The first volunteers joined this unique study in 1958.
1984 – NIA funds Alzheimer's Disease Centers (ADC) nationwide to conduct research at medical institutions focused on curing and preventing AD while improving care and diagnosis.
November 14, 1986 – P.L. 99-660, section 951-952, authorizes the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center as a part of a broad program to distribute information about Alzheimer's disease to health professionals, patients and their families, and the general public.
November 4, 1988 – P.L. 100-607 establishes the Geriatric Research and Training Centers (GRTC).
1988 – Congress authorizes NIA to make LEAD awards to researchers making significant contributions to Alzheimer's disease research.
1990 – The GRTCs are expanded and renamed the Claude D. Pepper Older American Independence Centers and charged with conducting research about diseases that threaten independent living.
1993 – Six Edward Roybal Centers for Research on Applied Gerontology are authorized to convert research findings into programs that improve the lives of older people and their families.
NIA funds six Exploratory Centers for Minority Aging and Health Promotion in collaboration with the NIH Office of Research on Minority Health.
1994 – Nine demography of aging centers are funded to provide research on health, economics, and aging, and to make more effective use of data from several national surveys of health, retirement, and long-term care.
1995 – Three Nathan Shock Centers of Excellence in Basic Biology of Aging are established to further the study of the basic processes of aging.
The Federal Task Force on Aging Research report is published containing nearly 200 specific recommendations for increased emphasis in ten general areas of research.
1999 – As part of NIA's 25th anniversary celebration, a strategic plan is formulated and made available for public comment. The plan addresses scientific topics holding the greatest promise for advancing knowledge in areas such as the basic biology of aging, geriatrics, and social and behavioral functioning.
Dr. Hodes was appointed NIA director on May 27, 1993. He was born on December 31, 1943, in New York City. He received his B.A. from Yale University (summa cum laude) in 1965 and his M.D. from Harvard Medical School (magna cum laude) in 1971.
His postgraduate training included an internship and residency at Massachusetts General Hospital department of medicine. Before attending medical school, he was a research fellow at the Karolinska Institute in Stockholm, Sweden. Before joining NIA, he was senior investigator and chief of the immune regulation section at NCI's Experimental Immunology Branch.
In 1997 Dr. Hodes was elected as a fellow of the American Association for the Advancement of Science. He received a PHS Commendation Medal in 1977, a PHS Outstanding Service Medal in 1988, and a PHS Distinguished Service Medal in 1996. In 1999 Dr. Hodes was elected to membership in the Institute of Medicine of the National Academy of Sciences.
NIA's Intramural Research Program (IRP) comprises eleven scientific laboratories, a clinical research branch and a research resources branch that include the scientific disciplines of biochemistry, cell and molecular biology, structural biology, genetics, behavioral sciences, epidemiology, statistics, and clinical research and the medical disciplines of neurobiology, immunology, endocrinology, cardiology, rheumatology, hematology, oncology, and gerontology. Medical problems associated with aging are pursued in-depth using the tools of modern laboratory and clinical research. The central focus of research is the understanding of age-related changes in physiology and the ability to adapt to environmental stress. This understanding is then applied to developing insight about the pathophysiology of age-related diseases. The program seeks to understand the changes associated with healthy aging and to define the criteria for evaluating when any change becomes pathologic. Thus, not only are the common age-related diseases under study (e.g., Alzheimer's disease, atherosclerosis, osteoarthritis, diabetes, cancer), but the determinants of healthy aging are also being defined.
Most IRP research is conducted at the Gerontology Research Center in Baltimore, Maryland. The section of Brain Physiology and Metabolism and the Laboratory of Neurogenetics are located in the Clinical Center on the NIH main campus in Bethesda, and the Laboratory of Epidemiology, Demography & Biometry is located in the Gateway Building in Bethesda.
The Laboratory of Cellular and Molecular Biology (LCMB) includes scientists formerly in the Laboratory of Biological Chemistry (LBC). The name was changed to better reflect the general interests of the group and the nature of ongoing studies. The interests of the LCMB cover a wide range of topics devoted to understanding biochemical and molecular events contributing to the aging process, and to the development of age-related disabilities and diseases. The LCMB has five research programs. A common goal of these programs is the elucidation of critical events associated with various age-related deficits that could serve as targets for therapeutic strategies aimed at preventing or delaying the onset of disabilities and disease processes. These research programs, each of which is headed by either a tenure-track scientist or a senior investigator, are the T Lymphocyte Signaling Unit, the Stress Signaling Unit, the Cell Cycle Control Unit, the Cancer Molecular Genetics Unit, and the DNA Repair Unit. Major areas of emphasis common to the individual programs include: 1) the elucidation of signal transduction processes and genes involved in regulating cellular responses to environmental signals such as growth factors, cytokines, and stress stimuli; 2) the determination of mechanisms contributing to the maintenance of cellular homeostasis and cell cycle control; 3) the contribution of dysregulated gene expression or loss of critical gene functions to the development of cancer; and 4) the role of DNA damage and repair in age and age-related disease. These processes have direct relevance to our understanding of critical events associated with various age-related deficits and/or development of age-related diseases including cancer. The ultimate goal of the programs is to uncover knowledge that can be applied to prevent or delay the onset of age-related disabilities and disease processes, and/or provide new strategies for their treatment. While the individual research programs within the LCMB generally function as independent groups, they are highly interactive, conduct twice monthly joint meetings, and engage in collaborative projects. Combined, the programs within the LCMB provide extensive and broad expertise in the areas of biochemistry, cellular and molecular biology, and genetics. Specialized expertise in a variety of approaches used to analyze or manipulate gene expression is also available within the LCMB. The LCMB is equipped with state-of-the-art instrumentation and an extensive computer network.
The Laboratory of Cardiovascular Science (LCS), established in 1985 is presently organized into two sections: Cardiac Function and Behavioral Hypertension. The Cardiac Function Section, which comprised the entire LCS at its incipience, is organized into nine functional units: the Cardiovascular Gene Therapy Unit, the Cardiovascular Biology Unit (Cardiac and Vascular Groups), the Calcium Signaling Unit, the Cardioprotection Unit, the Cellular Biophysics Unit, the Hypertension Unit, the Receptor Signaling Unit, the Human Cardiovascular Studies, and the Molecular Cardiology Unit. The Behavioral Hypertension Section was formerly part of the Laboratory of Behavioral Science and joined LCS in 1997.
The overall goals of the Laboratory of Cardiovascular Sciences 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 the chemical nature and sequence of intermediate reactions controlling the movement of ions through ionic channels and pumps present in myocardium, and how these are affected by aging and disease; (5) to determine mechanisms that govern neuro-hormonal behavioral aspects of hypertension; (6) to determine mechanisms of normal and abnormal function of vascular smooth muscle and endothelial cells; and (7) to establish the potentials and limitations of new therapeutic approaches such as gene transfer techniques. 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. In the LCS environment, discoveries are integrated within and among individual research areas, and many projects become multi-faceted, spanning the range from humans to molecules.
The Laboratory of Clinical Investigation (LCI) conducts research on age changes and mechanisms underlying these changes in humans, laboratory animals, cellular, and molecular systems. It comprises five sections and two units: the Bioanalytical Chemistry/Drug Discovery Section, the Diabetes Section, the Hematology/Oncology Section with the Cancer Immunology Unit, the Metabolism Section, the Molecular and Clinical Pharmacology Section, and the Nuclear Magnetic Resonance Unit. The interests and goals of the LCI are most broadly defined as the identification of potential therapeutic targets for the treatment of age-related disease. The mission of LCI is to carry out the research needed to move these targets to drugs and treatments that can then be developed for clinical therapeutics. The Bioanalytical Chemistry/Drug Discovery Section studies receptor-ligand interactions using molecular modeling and immobilized receptor columns to characterize drug-receptor, drug-enzyme, and drug-transporter interactions to develop screening methods for drug candidates. It serves as a bioanalytical core for measurement of drugs and metabolites obtained during clinical and preclinical studies, and as a resource for structural characterization of large protein molecules. It has also begun the study of treatment of wasting syndromes (cancer cachexia) using enhancers of intermediary metabolism. The Diabetes Section studies mechanisms of pancreatic islet cell differentiation and has identified receptors of the gut peptides GLP-1 and GIP as therapeutic targets for the development of insulinotropic agents. Cellular, animal, and clinical studies are underway to identify potential new drugs that target these receptors for the treatment of type 2 diabetes mellitus. In addition studies of the molecular basis of insulin receptor signaling are undertaken to better understand changes in insulin signaling that occur in diabetes. The Hematology/Oncology Section studies tumor suppressor genes, and seeks to identify, explore, and conduct translation research on new therapeutic targets that are promising for the aging cancer patient. The Cancer Immunology Unit studies mechanisms of lymphocyte signaling and activation, and is clinically evaluating the use of bryostatin-1 for the treatment of cancer. It will begin to utilize 'mini' bone marrow transplantation in combination with other treatments to improve cancer treatments in the aged patient. The Metabolism Section studies the utility of diagnostic criteria for diabetes and the metabolic syndrome using the BLSA database and other longitudinal study sets. The Molecular and Clinical Pharmacology Section studies mechanisms of calcium channel gating in the L-type calcium channel, to define the effects of age and disease on the expression of splice variants and function of this channel, and to study the structural mechanisms that this channel transmits its signal to other cellular signaling and effector pathways. These studies include study of clinical surgical tissue to link the molecular findings to human atherosclerotic disease. In addition clinical studies of the effect of genetic polymorphisms of endothelial nitric oxide synthase and angiotensin converting enzyme on forearm vascular reactivity, heart rate variability and drug responses are underway. Clinical and laboratory studies of the role of muscle atrophy in the evolution of osteoarthritis are also underway. The Nuclear Magnetic Resonance Unit studies connective tissue biophysics (whole cartilage, chrondrocytes in culture, and in vivo cartilage imaging), muscle metabolism under a variety of pharmacological and physiological conditions, and methodology development in imaging and spectroscopy. In vivo NMR is also conducted to define the phenotype of transgenic animals.
The Laboratory of Epidemiology, Demography, and Biometry (LEDB) conducts research on aging and age-associated diseases and conditions using population-based epidemiologic and biometric methods. Laboratory staff work collaboratively both within and among four sections: the Epidemiology and Demography Section, the Neuroepidemiology Section, the Geriatric Epidemiology Section, and the Biometry Section and with other NIA and outside investigators. The mission of LEDB is to elucidate the etiology of diseases of old age by combining epidemiologic data with information from other disciplines; evaluate the consistency of epidemiologic data with etiologic hypotheses developed either clinically or experimentally; and to provide the basis for developing and evaluating preventive procedures and public health practices. These general principles have guided a research agenda that emphasizes three important and interrelated areas: Physical Function and Disability, Cognitive Function and Dementia, and Age-associated Diseases and Conditions - including successful or effective aging. In each area, studies are influenced by results of analytic efforts of current LEDB-sponsored studies and by opportunities created by advances in biology. The Epidemiology and Demography Section plans and conducts studies on chronic diseases, functional status and disability in the older population. The Neuroepidemiology Section conducts interdisciplinary research on the association of genetic, molecular, and behavioral factors in relation to brain disease in old age. The Geriatric Epidemiology Section carries out interdisciplinary studies of the association of molecular and genetic risk factors with health outcomes in old age, including discrete diseases, disability and mortality. The Biometry Section conducts research in the mathematical, statistical and numerical aspects of aging and health. This section provides statistical consulting, computing, graphics, and data management services to the other units within LEDB. Senior LEDB staff consult with other components within the IRP, NIA, other NIH Institutes, other Government agencies, and the private sector. LEDB research interests use data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE), the Women's Health and Aging Study (WHAS), the Honolulu-Asia Aging Study (HAAS), Health and Body Composition (Health ABC) Study; InCHIANTI Study; Veterans' Study of Memory in Aging (VSMA); the MacArthur Studies of Successful Aging, and other epidemiologic studies.
The Laboratory of Experimental Gerontology is a new laboratory formed to create and supervise research in experimental models focused on interventions that retard aging processes. The laboratory currently comprises the Behavioral Neuroscience Section (BNS) and a Nutritional and Molecular Physiology Unit (NMPU); however, new organizational units are planned. A major project within the NMPU involves a longitudinal study to assess the beneficial effects of calorie restriction on aging in nonhuman primates. Other studies conducted in this unit utilize in vivo rodent models and in vitro cellular models to identify protective mechanisms invoked by calorie restriction. The LEG will also participate in a newly created program coordinated with the NIA extramural program designed to evaluate various aging interventions (pharmaceuticals, hormones, dietary supplements, genes) in mouse models to assess effects in a standardized fashion on lifespan, pathology, and functional capacity at older ages. Within the BNS, research is directed toward developing behavioral assays of aging in rodents and nonhuman primates with focus on motor and memory performance. Additional projects in the BNS involve identifying mechanisms of age-related decline in motor and memory performance and developing pharmacological, genetic, and nutritional interventions that improve function in the aging brain.
The Laboratory of Genetics (LG) comprises six units, with a Human Genetics Section; a Human Genetics and Integrative Medicine Section; a Developmental Genomics and Aging Section; a Transcription Remodeling and Regulation Unit, a Gene Recovery and Analysis Unit; and an Image Informatics and Computational Biology Unit. The interests of the laboratory are based on the view that aging has genetic determinants as an integrated part of human development, with a profound dependence on the interplay of synthetic and degradative processes that are initiated in utero. Major studies include: 1) transitions between immortal and mortal cells, such as the transition of immortal embryonic stem cells to mortal differentiating cells that is a fundamental feature of the initiation of aging in metazoans; 2) 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 examples of skin appendage, connective tissue, and ovarian follicle development are being studied; and 3) genes involved in embryonic events that prefigure aging-related phenomena. This includes studies of overgrowth syndromes, in which the set-point of size of tissues and organs is determined in fetal life, and 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. 4) Genes involved in embryonic events that prefigure aging-related phenomena. For example, the Human Genetics Unit is involved in studies of overgrowth syndromes, in which the set point of size of tissues and organs is determined in fetal life; 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; and studies by the HGIM focus on characteristics of heritable disorders of connective tissue including Ehlers-Danlos and Stickler syndromes, and various forms of dwarfism. 5) Genes involved in chromatin remodeling. The Transcription Remodeling and Regulation Unit is studying the action of the components of nuclear complexes that regulate chromatin accessibility and are affected in diseases, like Rett Syndrome, that correspondingly involve problems in chromatin structure and function. 6) The genetics of aging-related complex conditions is being approached by interactive studies of the "founder" population in Sardinia. Initial phenotypes to be studied along with epidemiological factors include arterial stiffness, selected psychiatric/psychological traits. For this project investigators from Cardiovascular Sciences (Edward Lakatta and Angelo Scuteri), Personality and Cognition (Paul Costa, Antonio Terracciano, and Alan Zonderman) are working with Antonio Cao and Giuseppe Pilia, human geneticists at the University of Cagliari, Sardinia. The Laboratory is equipped with state-of-the-art resources for genomic approaches in the Gene Recovery and Analysis Unit, including large-insert clones and recovery methods, high throughput sequencing, and nuclear fractionation; and the Developmental Genomics and Aging Section has built large cohorts of genes based on its capacity to make and analyze high-quality cDNA libraries from very few cells - for example, from subregions of embryos. An extension of technology is now being assessed in a major effort by the Image Informatics and Computational Biology Unit, devoted to comparative analyses of microscopic images, including database and algorithm development, to investigate protein distribution during cell division and tissue formation, and to facilitate automated screening for mutants.
The Laboratory of Immunology (LI) conducts studies to provide a greater understanding of the biological, biochemical, and molecular alterations in immune function that occur within individuals during both normal and pathology-associated aging processes. The Laboratory includes the Clinical Immunology Section, the Lymphocyte Differentiation Unit, and the Lymphocyte Cell Biology Unit. The common goal of these research programs is the elucidation of the age-related deficits in immune function that could be potentially targeted by various therapeutic strategies. The Clinical Immunology Section has concentrated its efforts on five major areas of research which include: (1) the molecular analysis of differentially-regulated genes involved in lymphoid organ and cell development, differentiation, and activation; (2) the study and use of biological response modifiers such as cytokines and hormones to optimize and control leukocyte trafficking, activation, and organ engraftment in normal and aging hosts; (3) the induction of antigen-specific tolerance for use in transplantation and autoimmunity; (4) the role of cholesterol and lipid rafts in cellular activation, trafficking, and HIV infectivity; and (5) the cellular and molecular dynamics involved in thymic involution and regeneration. The research interests of the Lymphocyte Differentiation Unit are focused mainly in three areas: (1) the molecular and cellular mechanisms of immunological memory; (2) the roles of telomere and telomerase in lymphocyte function, replicative lifespan, and aging; and (3) the mechanisms of age-associated loss of learning and memory formation in rodent. The research interests of the Lymphocyte Cell Biology Unit are focused in three major areas: (1) the role of T cell costimulatory pathways in the generation of GVHD and T-cell tolerance; (2) the factors involved in the regulation of tumor cell growth and division; and (3) the mechanisms of tumor- induced immunosuppression.
The Laboratory of Molecular Gerontology (LMG) investigates DNA related mechanisms such as genomic instability, DNA repair, DNA replication, and transcription. The DNA Repair Section examines the role of the increased DNA damage accumulation in senescence as the major molecular change with aging. The goal is to understand the underlying mechanisms involved in DNA damage formation and it’s processing as well as the changes that take place with aging that make aging cells susceptible to cancer. Investigative focus is placed on investigating the molecular mechanisms involved in DNA repair and in genomic instability in normal, senescent and cancer cells. The human premature aging syndromes are primary targets of investigation. Studies are focused on the molecular functions and protein interactions of the premature aging proteins, Werner syndrome and Cockayne syndrome. The DNA Helicases Unit focuses on the roles of DNA helicases in genomic stability. The growing number of DNA helicases implicated in human disease suggests that these enzymes have vital specialized roles during replication, DNA repair, recombination, and transcription. RecQ DNA helicases are of particular interest because the human hereditary disorders Werner syndrome (WS), Bloom syndrome, and Rothmund-Thomson syndrome all arise from mutations in genes of the RecQ helicase family. This unit focuses its efforts on understanding the cellular and molecular defects of WS, a premature aging disorder characterized by genomic instability. The Gene Targeting Section is developing oligonucleotides that can form a three-stranded DNA structure called a triple helix. The third strand lies in the major groove of an intact double helix and is stabilized by hydrogen bonds between the bases in the third strand and the purine bases in the duplex. These oligonucleotides can be linked to DNA reactive compounds and site-specific modification of DNA with these oligo-reagent conjugates has been demonstrated by many groups. Due to recent advances from this group of investigators, this approach can now be used to deliver additional DNA reactive compounds to specific genomic locations. Eventually this approach will be used to modulate genomic sequences with targeted gene knockout as a specific application. The Antibody Diversity Unit investigates the mechanism of somatic hypermutation. Somatic hypermutation of variable genes, which encode a portion of immunoglobulin molecules, occurs at a frequency that is a million times greater than mutation in other genes. Evidence points to a process that involves DNA repair events at sites of targeted strand breaks. In vertebrate cells, there are many recently identified DNA polymerases that inaccurately copy templates. This unit is studying the roles of DNA polymerases zeta, eta, and iota in the mechanism. In addition, work from this group includes examination of whether aging alters the frequency and pattern of hypermutation. The Unit of Structure and Function in base excision Repair investigates the mechanism involved in base excision repair, the removal of oxidative DNA lesions. The functions of the individual proteins are studied and their interactions are investigated. The approach is a combination of protein structure and function and with a view to how mutations and alterations in these proteins in the population change their function and cause disease. The Unit of Oxidative DNA damage processing and mitochondrial function focuses on mitochondrial DNA, and the studies seek to investigate the basis for the mitochondrial hypothesis of aging which states that accumulation of DNA damage with aging leads to the phenotypical changes that we observe in senescence and age-associated disease. The mechanisms of removal of oxidative DNA damage from mitochondria are investigated and how they are affected by increasing age or disease processes.
The overarching goal of research efforts in the Laboratory of Neurosciences (LNS) is to understand the cellular and molecular mechanisms that regulate neuronal plasticity and survival in the context of aging and age-related disease. It is assumed that there are fundamental mechanisms of aging that are shared among organisms at different levels of the phylogenetic tree, and that the lifespan of individuals is determined by the genes they express and environmental factors they encounter. A major focus of ongoing projects is to identify the factors that determine whether aging of the nervous system is successful, or whether a disease develops. There is therefore a strong emphasis placed on elucidating cellular and molecular alterations that lead to neuronal dysfunction and degeneration in disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke and amyotrophic lateral sclerosis (ALS). This is accomplished by studying human patients, cell culture and animal models relevant to human disease. Among the major areas of investigation are the signal transduction mechanisms that normally regulate cellular oxyradical, energy and ion homeostasis, and how they may be altered during aging and in age-related neurodegenerative disorders. Knowledge gained in such basic research is then being used in preclinical studies to develop approaches (diet, lifestyle, drugs and cell therapy) for preventing and treating these disorders. LNS comprises five sections which include: the Cellular and Molecular Neurosciences Section, the Developmental Neurobiology Section, the Drug Design and Development Section, the Synaptic Physiology Unit, and the Invertebrate Molecular Genetics Unit.
The fundamental scientific paradigm guiding research in the Laboratory of Personality and Cognition (LPC) is the analysis of individual differences. Few phenomena are more basic than the fact that human beings differ - in health, in rates of aging, in cognitive ability, in personality, in happiness, and in life satisfaction. The LPC conducts basic and clinical research on individual differences in cognitive and personality processes and traits. The laboratory investigates the influence of age on these variables and their reciprocal influence on health, well-being, and adaptation. It employs longitudinal, experimental, and epidemiological methods in the analysis of psychological and psychosocial issues of aging, including health and illness, predictors of intellectual competence and decline, models of adult personality, and correlates of disease risk factors. The Personality, Stress, and Coping Section has conducted systematic basic research in personality guided by the Five Factor Model (FFM) which asserts that personality traits can be understood as aspects of five factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. The FFM is now the prevailing conception of personality in psychological research. The unit on Emotions and Psychophysiology conducts research on the role of emotions and psychophysiology processes related to psychological adaptation and health. The Cognition Section conducts studies that attempt to distinguish pathological from healthy, age-related cognitive changes in a broad range of cognitive tasks, including short-term and long-term memory, visual/spatial rotation, attention, and decision tasks. Performance of Baltimore Longitudinal Study on Aging (BLSA) participants on the Benton Visual Retention Test has led to the test's identification as a potential early marker for Alzheimer's disease. That finding is being followed up using neuroimaging techniques. Work is ongoing to determine whether estrogen provides a protective effect on memory.
The goal of the Laboratory of Neurogenetics is to develop an understanding of neurodegenerative and neurologic diseases (Alzheimer's disease, Parkinson's disease, dystonia, ALS and stroke are current areas of research) based on genetic analysis. To this end, the group has four sections and two cores: a Clinical Section (shared with NINDS) who co-ordinate the identification and assessment of families and cases with the disease we are working on, a Genetic Section who spearhead gene and mutation identification for these diseases, a Cell Biology Section whose role is to define the cellular effects of pathogenic mutation and a Transgenic Section (for which recruitment is still ongoing) which will use mutant genes to develop animal models of disease. Underpinning this work is a Genetic Linkage Core which provides high throughput genotyping and sequencing and a Bioinformatics Core whose role is to develop our data in the context of the vast array of genomic and biologic data now available through computational analysis. The lab is in Bethesda and shares many projects with the Laboratory of Neurogenetics (NINDS), the Laboratory of Genetics (NHGRI) and the Laboratory of Epidemiology (NIA).
The Molecular Dynamics Section focuses on the interplay between structure and dynamics and how these influence biological function. The section is presently involved in studying the structural and dynamic factors in hemoglobin, which regulate the binding of oxygen as well as autoxidation with its associated release of superoxide. The finding that autoxidation of hemoglobin is appreciably enhanced at reduced oxygen pressures, has led to the proposal of a novel method for producing oxyradicals under hypoxic conditions. Studies are being performed on erythrocytes, interaction of erythrocytes with other tissues and with whole animals to determine to what extent this mechanism contributes to the pathophysiology of aging.
The Brain Physiology and Metabolism Section (BPMS) studies brain function, metabolism, and structure with regard to aging and disease, including Alzheimer's disease. Investigators are currently working to improve the sensitivity and specificity of diagnostic tools including Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), structural magnetic resonance imaging, magnetic resonance spectroscopy, as well as neuropsychological and behavioral assessment.
The Clinical Research Branch (CRB) is a newly formed Branch organized into the Office of the Clinical Director and five sections (Longitudinal Studies Section, Health Disparities Research Section, Translational Research and Medical Services Section, Clinical Support Section and the Clinical Information and Data Management Section). The overall goals of the CRB are: 1) the conduct of major longitudinal studies of aging including the BLSA and HANDLS studies and 2) to support and carry out translational research in the major areas of clinical research focus of NIA-IRP laboratories including longitudinal studies and interventional trials with a focus on cardiology, neurology, endocrinology and oncology disease areas. In the latter, the branch: 1) provides the infrastructure needed to promote high quality clinical research and to ensure patient safety including: protocol review, clinic infrastructure, nursing and physician support, clinical informatics, data and safety management; 2) monitors and maintains quality assurance of the intramural clinical research program; 3) develops and implements clinical program priorities, allocates clinical resources; 4) integrates the established research themes and projects with clinical relevance from various IRP laboratories and branches; 5) evaluates program effectiveness and represents the IRP in management and scientific decision-making meetings within the Institute; 6) coordinates the credentialing of health care providers within the Institute; 7) coordinates and provides clinical research training for NIA staff and fellows and 8) develops novel approaches for carrying out translational research in an efficient and cost-effective manner. Ongoing research projects within the branch include: two large longitudinal studies, the Baltimore Longitudinal Study on Aging (BLSA) and the Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS); studies of factors predisposing patients to osteoarthritis and evaluation of muscular changes contributing to disability from this disease and studies of neuromuscular/ strength changes with aging. The NIA IRP Cytapheresis Unit is also a part of CRB. This unit conducts cytapheresis on BLSA participants and other normal volunteers providing important clinical research materials (T-cells, B-cells) to program investigators examining immunosenescence, the role of telomeres in human aging and other age related research. In addition, the CRB supports all other clinical studies conducted within the NIA-IRP through provision of Protocol Support, Pharmacy support and Clinical Core Laboratory support under the Office of the Clinical Director and Nursing support under the Clinical Support Section of the Branch.
Office of Extramural Affairs
The Office of Extramural Affairs (OEA) manages NIA's extramural program activities. It often is the first point of contact for applicants requesting information on how to apply for federal support or who wish to know if their research ideas may be of interest to NIA. The OEA coordinates NIA's extramural programs and ensures that policies and procedures are implemented in a uniform and fair way. The Office has responsibility for oversight of grants and contract administration, scientific review, and committee management functions. The Office serves as primary liaison for NIA with the NIH Office of Extramural Research, and with other institutes that share research interests. It also has primary responsibility for NIA's extramural training programs, career development programs, small business initiatives, and other special programs. The Office handles appeals, and scientific integrity and other ethical issues involved in the conduct of research. The OEA organizes meetings of the National Advisory Council on Aging (NACA) and meetings of related groups. OEA has central responsibility for research training and career development activities at the institute, including policies related to different mechanisms, eligibility, and initiatives to increase the number of underrepresented students and researchers trained in aging research.
The Scientific Review Office (SRO) of the OEA is responsible for initial peer review of specific research applications assigned to the NIA. These include applications for grants to Centers, for program project initiatives, and for training and career development. Members of NIA's four review panels that correspond to the Institute's program areas and members of the Institute's special emphasis panels include non-government scientists who are themselves grantees and who are expert in the scientific areas of the applications they review.
While the SRO interacts with applicants prior to the award of grants, the Grants and Contracts Management Office (GCMO) works with scientists and institutional research administrators to issue, manage, and close awards when the research is completed. GCMO staff members provide guidance on administrative and fiscal policies and practices for the investigator and for the institutional research administrators. For example, they address questions about allowable costs and about major changes in staff or content of the research project. The GCMO has legal responsibility for the fiscal management of the Institute's extramural grants and contracts.
External Scientific Review
In support of research, research training, and career development related to aging, the NIA awards grants to universities, hospitals, and research organizations throughout the U.S. and abroad. Approximately 80 percent of the funds appropriated to the NIA are disbursed through these extramural awards. Competition for this funding is very high; for example, over the past ten years, NIA was able to fund fewer than one in three of the research project grant applications it received. To ensure that the research funded is of the highest quality and serves the health needs of the nation, peer review committees comprised of external scientific experts are brought together to review proposed and ongoing research.
Extramural Grant Review
Extramural research investigators trigger the grant review process by submitting grant applications to the NIH Center for Scientific Review (CSR). Initial review of applications may be assigned to a Center review group or to NIA's initial review committee which reviews program project, center, research career, small, and institutional training grant applications, as well as applications submitted in response to RFAs issued by the NIA.
Applications clearly within NIA's mandate are forwarded to NIA for funding consideration. Whether the applications are reviewed at the Center for Scientific Review or at the NIA, committees of experts, including NIH grantees, assess the quality and originality of the proposed science. Reviewers also assess applications for the qualifications of the investigators, quality of the proposed facilities, treatment of animal models, if relevant, and, for research involving humans, the proposed plans for recruiting women and minorities to the studies. The judgment of the group on these parameters is summarized in a report (summary statement) and overall rating (priority score) of the application. These reports are provided to the applicants and to NIA officials. Among the applications assigned to the NIA, approximately the top half, as judged by initial review, are given a second level of review by the National Advisory Council on Aging.
National Advisory Council on Aging
Congress created the National Advisory Council on Aging (NACA) to provide advice on programmatic and policy matters; specifically:
Grant applications over $50,000 must receive Council approval to be eligible for funding. In its deliberations, the NACA reviews summary statements to evaluate the fairness and appropriateness of the initial review of grant applications, and considers the scientific and public importance of the proposed work. In cases in which the applicant or NIA staff has concerns about the initial review of the application (special actions), NACA members can evaluate these concerns.
Council members also serve as a conduit for insights into the concerns and opinions of the research community, and assist in keeping the scientific community, Congress, and the public knowledgeable about the activities of the NIA.
The NACA meets three times each year, typically for a period of two days to review applications for grants and cooperative agreements for research and training. The group recommends funding of research applications that show significant promise of a) improving the quality of life and health care for the aged; or b) making valuable contributions to our scientific knowledge of the aging process.
The NACA consists of 18 members appointed by the DHHS Secretary and five non-voting ex officio members. Of the 18 appointed members, 12 are leading representatives of the health and scientific disciplines and are leaders in the fields of public health and the behavioral or social sciences relevant to the activities of the NIA, particularly with respect to biological and medical sciences relating to aging and public health. Six of the members are leaders from the general public in the fields of public policy, law, health policy, economics, and management. Members are invited to serve for overlapping four-year terms.
Once the Council provides its recommendations, the NIA Director may approve payment of applications that have been favorably reviewed and for which sufficient funds are available. Primary weight is given to the scientific quality of the application as judged by initial peer review. Consideration is also given to the proposed research's relevance to NIA priorities and to the timeliness of the research.
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. The objective of the Animal Models Program is to identify and develop new animal models, both mammalian and lower organism, for use in aging research. This includes research on rats, mice, birds, fish, rabbits, non-human primates, insects, nematodes and yeast. Mutant and genetically engineered rodent models of both normal aging and specific age-related pathologies are of particular interest.
Cardiovascular Biology. The objectives of the Cardiovascular Biology Program are to support basic research on age-related changes in cardiovascular function, e.g. gene expression, and on factors affecting cell death in heart tissue.
Cell Structure and Function Program. The objectives of the Cell Structure and Function Program are to support research on the molecular basis of age-related changes in signal transduction mechanisms; microenvironment - ECM; replicative senescence/apoptosis/cancer; membranes and membrane receptors, and protein structure and function.
Endocrinology Program. Hormones secreted by the endocrine system play major roles in informing various organs of the status of other organ systems and in coordinating the functioning of various organ systems. As humans and various animal models age, average serum levels of some of these hormones decline while others rise, changing the overall hormonal milieu of the organism. Also, the sensitivity of some intracellular signaling pathways responsive to endocrine factors change with age, altering tissue response to hormonal signals. The purpose of the endocrinology of aging program is to support basic molecular and cellular research into the causes and effects of age-related changes in the endocrine system of humans and various animal models. Areas of investigation in this program include age-related changes in hormone production, metabolism, and action; Type II diabetes; reproductive aging: biology of menopause and animal models of menopause; age-related changes in control of prostate growth; and endocrine aspects of age-dependent tumors.
Genetics Program. The objectives of the Genetics Program are to support research on identification and characterization of longevity assurance genes (LAGs) and senescence assurance genes (SAGs); genome stability; telomere biology; genomics; mouse mutagenesis; single nucleotide polymorphisms/genetic epidemiology; and Werner syndrome.
Immunology Program. Changes in the immune system of older people may contribute to the increased incidence of infection and cancer in the elderly. Research directed towards understanding the age-related regulation of immune function in health and disease is supported by BAP. Areas of investigation in this program include regulation of lymphocyte proliferation; regulation of immune specificity; response of immune system to biochemical stimuli; autoimmune disease and other immunopathology; endocrine control of immune function; molecular basis of the age-related decline in immune function; and interventions to retard and/or correct age-related decline in immune function.
Metabolic Regulation. Areas of investigation in the Metabolic Regulation Program include nutrition and metabolism; age-related changes in mitochondrial function/mitochondrial dysfunction; mechanism of life span extension by caloric restriction; and generation of free radicals and oxidative stress.
Musculoskeletal Biology. The age-related change of function of various physiologic systems often negatively impacts the health of the elderly. The purpose of this program is to support high quality basic molecular and cellular research to understand the causes and effects of these changes, thereby encouraging the development of preventative and interventional strategies to extend the health span of the elderly. Areas of investigation in this program include age-related changes in osteoblast and osteoclast function and bone matrix; age-related changes in muscle structure and function; age-related changes in cartilage, connective tissue and skin; age-related changes in wound healing; molecular mechanisms of the above age-related changes; and molecular basis of osteoporosis and osteoarthritis.
The Biology of Aging Program also includes the Office of Biological Resources and Resource Development. Because most investigators have neither the facilities nor the resources needed to develop and maintain colonies of aged animals in a barrier facility, the NIA provides support for both rat and mouse colonies for use by the scientific community. The cost of these animals is partially subsidized by the NIA through contracts. Other NIA resources managed by this office include colonies of rhesus macaque monkeys, an Aged cell bank, and a Genetic Stock Center for nematode mutant strains.
Geriatrics and Clinical Gerontology Program
The NIA Geriatrics and Clinical Gerontology Program comprises three branches:
The Geriatrics Branch is focused primarily on health issues regarding the aged, and deals with research on disease and disability in older persons, including both specific conditions and issues related to multiple morbidity. Examples of current research areas addressed by this branch and future directions are:
The Clinical Gerontology Branch is focused primarily on clinically related issues regarding aging, and deals with research on aging changes over the life span. A major focus is on the determinants of rates of progression of age-related changes that affect disease risk, particularly those affecting risk for multiple age-related conditions. Examples of current areas addressed by this branch and future directions are:
The Clinical Trials Branch plans and administers clinical trials on age-related issues that require extensive specialized clinical trials expertise. Examples of current and possible future types of interventions for trials are:
Neuroscience and Neuropsychology of Aging Program
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 Branch fosters research on age-related cellular, molecular, and behavioral 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.
The Fundamental Neuroscience Section supports research at cellular, molecular, and behavioral levels that explore age-related structural and functional changes in brain.
The Integrative Neurobiology Section supports research on neural mechanisms underlying age-related changes in endocrine functions; neurodegenerative diseases of aging associated with infectious agents; and central nervous system, neuroendocrine system, and immune system interactions in aging.
The Sleep and Biological Rhythms Section focuses on studies of epidemiology, etiology, pathogenesis, diagnosis, treatment, and prevention of sleep disorders of older people, age-related mechanisms underlying sleep-wakefulness cycles and behavioral sequelae in the aged, and on biorhythmicity in the aging nervous system.
The Sensory Processes Section focuses on mechanisms of normal aging and disease-related alterations in visual, auditory, somatosensory, vestibular, and chemosensory functions, and pain from the level of the gene to the whole organism as well as epidemiological studies of populations.
The Motor Function Section supports research on proprioception, postural control, sensory motor integration, vestibular, and movement disorders in aging, including Parkinson's disease.
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 cognitive decline, mild cognitive impairment, and Alzheimer's disease including prevalence, incidence, and risk and protective factors and on models for large-area registries for Alzheimer's disease.
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, progression, and response to treatment.
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 programs, which provide a multifaceted approach to research on Alzheimer's disease, including clinical and other core services, neuropathological evaluation, basic and clinical research, professional and public information, and educational activities. It also supports the National Alzheimer's Coordinating Center.
Neuropsychology of Aging. The Neuropsychology of Aging Branch emphasizes research, including the use of animal models, 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, and the integration of these approaches, to understanding these structural and dynamic brain changes and adaptations is encouraged.
Behavioral and Social Research Program
This program supports basic social and behavioral research and research training on the processes of aging at both the individual and societal level. It focuses on how people change over the adult life course, on the interrelationships between older people and social institutions, and on the societal impact of the changing age-composition of the population. Emphasis is placed upon the dynamic interplay between the aging of individuals and their changing biomedical, social and physical environments and on multi-level interactions among psychological, physiological, social and cultural levels.
BSR supports research, training, the developing of research resources and methodologies to produce a scientific knowledge base for maximizing active life and health expectancy. This knowledge base is required for informed and effective public policy, professional practice, and everyday life, and BSR also encourages the translation of behavioral and social research into practical applications.
The BSR Program is administratively organized into two branches: (1) Individual Behavioral Processes and (2) Population and Social Processes, with substantial interactions between them. A section devoted to Research Resources and Development is housed within the Office of the Associate Director.
Individual Behavioral Processes Branch. This branch supports research and training on biopsychosocial processes linking health and behavior, cognitive functioning, human factors, and integrative approaches to the study of social, psychological, and physiological influences on health and well-being over the life course. Personality and social/interpersonal relationships are investigated as causal variables, and as mediators or moderators of the relationship between social/structural characteristics and health outcomes.
Population and Social Processes Branch. This branch supports research and training on the antecedents and impact of changing social, demographic, economic, and health characteristics of the older population. Research on the consequences of particular health care organizations and settings, and studies of the effects of other social institutions upon the health, well-being, and functioning of people in the middle and later years are supported. Comparative research is often appropriate, and interconnections with individual behavioral processes are encouraged.
The Office of Research Resources and Development (ORRD). This
Office replaces the Office of Demography of Aging that was established
in 1991. ORRD coordinates and implements initiatives related to research
data and resources. The Office manages the Health and Retirement Study
(HRS), the National Archive of Computerized Data on Aging (NACDA), and
all Interagency Agreements. ORRD also serves as the administrative site
for the Federal Interagency Forum on Aging-Related Statistics that was
established in 1986 to encourage cooperation among federal agencies responsible
for the collection, analysis, development, and dissemination of data on
the aging population.
1 Includes research
grants and research manpower development awards. Excludes research contracts.
|This page was last reviewed on June 22, 2005 .|
National Institutes of Health (NIH)