Biology of Aging Program:
Understanding Aging Processes, Health, and Longevity
Investigators supported by NIA’s Biology of Aging Program (BAP) seek to better understand the basic biological mechanisms underlying the process of aging and age-related diseases. Basic biochemical, genetic, and physiological studies are carried out primarily in animal models, including both mammals and non-mammalian organisms (e.g. flies, worms, and yeast). BAP’s goal is to provide the biological basis for interventions in the process of aging, which is the major risk factor for many chronic diseases affecting the American population.
In FY 2007, NIA began planning for a “Biology of Aging Summit” to review BAP’s current research portfolio, identify areas of opportunity, and facilitate the formulation of cohesive and comprehensive plans for the future. This conference will be held in FY 2008.
Budget Policy: The FY 2009 budget estimate for the Biology of Aging Program is $178,396,000, a decrease of $237,000 or .1 percent from the FY 2008 level of $178,633,000. Program objectives for FY 2009 include plans to:
- Continue the search for interventions that extend the lifespan. NIA is testing promising compounds in mice and other model systems with the long term goal of selecting for further development those most likely to have a beneficial effect in humans. An important component of this effort is the Intervention Testing Program (ITP), an NIA-supported project investigating treatments such as diets, pharmaceuticals, and nutritional supplements that have the potential to extend the lifespan and delay disease and dysfunction in a mouse model. Ten compounds are currently under study, and it is anticipated that up to three additional compounds will be added in 2008 and again in 2009.The ITP is the primary mechanism through which the NIA is working to achieve its most recently established GPRA goal, “By 2012, identify at least one candidate intervention that extends median life span in an animal model.”
- Increase our understanding of the aging immune system. A new initiative on “Membrane Associated Signaling Defects in Immune Cells with Aging” seeks to shed light on the cellular processes that may lead to impaired immune function in older people. In FY 2007, eight research grants were awarded; these grants will be active in FY 2009, and a new solicitation is under development for grant applications beyond FY 2009. NIA also collaborated with the National Institute of Allergy and Infectious Diseases on a June 2007 workshop to discuss recent research advances in our understanding of the underlying mechanisms that regulate age-related atrophy of the thymus, an organ that is critical to the healthy function of the immune system.
- Increase our understanding of the interactions among protein quality control systems in aging cells. Continuous turnover of cellular proteins is critical for maintaining healthy cell function and preventing cell death. In FY 2007, NIA solicited grant applications for research collaborations to increase our understanding of the interplay among various mechanisms responsible for the repair or removal of damaged, mutated, or misfolded proteins. Findings from this research may have implications for a number of age-related diseases, including neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Awards are planned for FY 2008 to run through FY 2009.
Behavioral and Social Research Program:
Understanding and Addressing the Behavioral, Emotional, and Social Dynamics of Aging
NIA’s Behavioral and Social Research Program (BSR) supports social and behavioral research to better understand the processes of aging at both the individual and societal level. Research areas include the behavioral, emotional, and social changes individuals undergo throughout the adult lifespan; interrelationships between older people and social institutions; and the societal impact of the changing age composition of the population. BSR also supports research training; development of research resources such as publicly available, cross-nationally comparable databases that support critical multidisciplinary behavioral and social research; and a knowledge base for the development of interventions to maximize active life and health expectancy.
In 2007, NIA commissioned an evaluation of its highly successful Demography of Aging Centers and Roybal Centers for Applied Gerontology. The evaluators were enthusiastic about the Centers’ activities and accomplishments; NIA plans to renew both programs in FY 2009. In addition, in February 2007, NIA partnered with the Department of State to host a Summit on Global Aging, which provided a unique and important opportunity to catalyze greater international dialogue and encourage coordinated international studies about the health, economic, social, and security implications of this important issue.
Budget Policy: The FY 2009 budget estimate for the Behavioral and Social Sciences Research Program is $171,706,000, a decrease of $227,000 or .1 percent from the FY 2008 level of $171,933,000. Program objectives for FY 2009 include plans to:
- Continue major demographic studies that provide important insights into social and economic trends. NIA supports long term studies of older Americans covering a wide range of topics, including retirement and economic status, caregiving, behavioral medicine, the dynamics of health and functional change at older ages, cognition, genetics, and long-term care. Notable studies include the ongoing Health and Retirement Study (HRS) (established 1992), the leading source of combined data on health and financial circumstances of Americans over age 50 and a valuable resource to follow and predict trends and help inform policies for an aging America. NIA also partners with the U.S. Census Bureau on joint demographic studies of the elderly population and the Federal Forum on Aging, which is composed of 13 federal departments and agencies, and collects, provides, and analyzes aging-related data.
- Support research initiatives to address financial challenges faced by American elders. Funding for two major initiatives in this area will continue through FY 2009. One initiative, “Developing Integrated Economic Models of Health and Retirement,” stimulates development of comprehensive econometric models of retirement from the labor force. The other focuses on the neuroeconomics of aging and supports research to examine the social, emotional, cognitive, motivational processes and neurobiological mechanisms of decision-making behavior in older people.
- Support development of new methods to collect, store, and share research data from longitudinal studies. Much of the data from NIA’s long term surveys is available to researchers in the behavioral and social sciences but has become more difficult to use over time due to complexity of longitudinal samples or the addition of new survey components. To make these data more widely available, a new NIA initiative seeks to develop and archive user-friendly public use data files from longitudinal surveys and behavioral interventions. NIA also supports efforts to ensure comparability of results from surveys from different countries, which will facilitate our understanding and ability to address the challenges of an aging society at the global level.
Neuroscience and Neuropsychology of Aging:
Understanding, Preventing, and Treating Cognitive Decline and Disability
NIA’s Neuroscience and Neuropsychology of Aging (NNA) Program supports a broad spectrum of research and training aimed at better understanding age-related normal and pathological changes in the structure and function of the nervous system and how such changes affect behavior. The basic mission is to expand knowledge on the aging nervous system to allow improvement in the quality of life of older people. This includes basic and clinical studies of the nervous system, clinical trials of treatments and preventive interventions for neurological disease, and epidemiological research to identify risk factors and to establish prevalence and incidence estimates of pathologic conditions. Additionally, it supports research relevant to those geriatric problems arising from psychiatric and neurological disorders associated with aging.
In October 2007, in partnership with the McKnight Brain Research Foundation and the Foundation for the National Institutes of Health, NIA held a Cognitive Aging Summit. The purpose of this major meeting was to bring together experts from a variety of research fields to discuss the latest advances in our understanding of age-related brain and behavioral changes. Recommendations from this conference will inform NIA’s research directions in the field of cognitive aging in the coming years.
Budget Policy: The FY 2009 budget estimate for the Neuroscience and Neuropsychology of Aging Program is $412,655,000, a decrease of $546,000 or .1 percent from the FY 2008 level of $413,201,000. Program objectives for FY 2009 include plans to:
- Continue to support high-quality research on Alzheimer’s disease (AD). Alzheimer’s disease is a major public health issue for the United States because of its enormous impact on individuals, families, the health care system, and society as a whole. NIA supports a robust portfolio that encompasses all areas of AD research, from the molecular underpinnings to cutting-edge diagnostic and treatment modalities. NIA will continue its preclinical drug development program (established 2005) and pilot trials initiative (established 1999), plus a cooperative agreement with the University of California, San Diego to conduct several new clinical trials of interventions to treat AD through the Alzheimer’s Disease Cooperative Study. In addition, NIA will continue work under the groundbreaking AD Neuroimaging Initiative, which reached its target enrollment during FY 2007, and the AD Genetics Initiative, which was established to facilitate identification of genes that contribute to late-onset AD, the more common form of the disease.
- Continue to fund a consortium to follow and evaluate individuals who are genetically predisposed to develop early-onset Alzheimer’s disease. Inherited early-onset AD is rare, accounting for fewer than one to five percent of all cases of the disease. However, disease onset and course are similar to those seen in the more common late-onset form of AD. Because there is a high probability that genetically-predisposed individuals will eventually develop AD, they represent an important population in which to study AD at its earliest pre-symptomatic stages and to evaluate possible preventive interventions. Funding for this consortium, which was a major recommendation resulting from NIA’s 2006 AD Summit, will begin in FY 2008, and it is anticipated that the consortium will be active during FY 2009.
- Continue research on neurological diseases and conditions other than AD that occur in older Americans, including Parkinson’s disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). This research is an important component of NIA’s portfolio. NIA-supported scientists have discovered a link between a mutated gene and a protein found in brain cells of people who suffer from FTD and ALS. The finding demonstrates for the first time a pathological pathway that results in cell death related to these diseases, and could eventually play a role in the design of new drug therapies. In FY 2009, NIA will continue research in these areas through investigator-initiated projects and through projects funded under relevant research solicitations.
Program Portrait: Cognitive Health and Aging
Although most people remain relatively alert and mentally able as they grow older, some loss of cognitive function is normal with advancing age. However, the mechanisms behind these cognitive losses are not fully understood, and interventions are needed to help older people maintain optimal brain health for as long as possible. With the aging of the U.S. population, the development of strategies to maintain cognitive health into late old age is becoming increasingly important.
A new focus on brain health, as opposed to the study of causes of specific brain diseases and dysfunction, has emerged in recent years and has become an increasingly important paradigm in neurosciences research. One NIH initiative to support the study of brain health is the Cognitive and Emotional Health Project (CEHP). Established in 2001 by NIA, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke, the goal of the CEHP is to coordinate and accelerate research leading to interventions for neurological health. One major effort has been the systematic review and critique of published literature on factors for cognitive and emotional health in the adult. Based on suggestions from the CEHP panel that conducted the evaluation of the published literature, the NIH Blueprint for Neuroscience Research awarded a contract in 2006 to develop an assessment tool to measure cognitive, emotional, motor and sensory function in large cohort studies. Other ongoing CEHP efforts include the development of a comprehensive online bibliography and a database of large longitudinal and epidemiological studies that have captured data on cognitive and emotional health risk and prevention factors. A perspective on CEHP and related research supported by NIA and NIH was published in the April 2007 supplementary issue of the journal Alzheimer’s and Dementia.
Studies of normal cognitive aging may also inform our understanding of cognitive dysfunction -- and vice versa. For example, low levels of AD pathology observed in the brains of those enjoying apparently normal aging, without cognitive abnormalities, could be early signs of the disease. Conversely, studies conducted under the Alzheimer’s Disease Neuroimaging Initiative might be particularly informative as we seek to better understand normal aging. This study aims to identify imaging and biochemical markers for “healthy” or normally functioning persons, for those with mild cognitive impairment (MCI), and for persons with AD or other dementias. Eventually, such markers will help to identify people at high risk for cognitive decline or dementia.
In October 2007, NIA, in partnership with the McKnight Brain Research Foundation and the Foundation for the National Institutes of Health, held a Cognitive Aging Summit. Participants in this advisory meeting generated innovative recommendations for advancing the field of cognitive aging research, with particular emphasis on ways to promote and maintain cognitive health and brain health in older adults. We anticipate that research initiatives stimulated by this meeting will be launched in FY 2009.
Geriatrics and Clinical Gerontology Program:
Reducing Disease and Disability among Older People
As we age, our risk for many other types of disease and/or disability increases dramatically. NIA’s Geriatrics and Clinical Gerontology (GCG) Program supports research on health, disease, and disability in the aged (other than neurodegeneration, which is the focus of the NNA Program). Areas of focus include age-related physical changes and their relationship to health outcomes, the maintenance of health and the development of disease, and specific age-related risk factors for disease. The program also plans and administers clinical trials.
In FY 2007, NIA issued a research solicitation for the renewal of the Claude D. Pepper Older American Independence Centers Program, the goal of which is to increase scientific knowledge leading to better ways to maintain or restore independence in older persons. Awards will be made in FY 2008.
Budget Policy: The FY 2009 budget estimate for the Geriatrics and Clinical Gerontology Program is $136,076,000, a decrease of $180,000 or .1 percent from the FY 2008 level of $136,256,000. Program objectives for FY 2009 include plans to:
- Initiate studies of venous and arterial thrombosis in the elderly. Older age is associated with a dramatic increase in venous and arterial thrombosis (the development of dangerous blood clots in the veins and arteries). However, the biologic mechanisms for this increased risk are poorly understood. A new initiative is exploring the biological mechanisms, epidemiology, pathophysiology, and clinical aspects (diagnosis, treatment, and prevention) of this common condition. Grants awarded under this initiative will be active in FY 2009.
- Continue research on anemia in the elderly. Anemia is common among older people; however, over halfthe cases of anemia in older adults occur without a clearly identifiable cause. An ongoing program supports research to better understand the epidemiology, pathophysiology, and clinical aspects of anemia in the elderly. In addition, an NIA Advisory Workshop on clinical trial issues in studying anemia in older patients was held in October 2007, resulting in the development of a research consortium to facilitate the establishment of a research program in anemia in the elderly and stimulate clinical studies of promising new approaches to its management. NIA plans to release a new solicitation inviting applications for this consortium in early 2008, and awards will be active in FY 2009.
- Identify childhood factors that may exert a protective effect on health later in life. Some studies have suggested the existence of physical factors, such as those that contribute to tissue maintenance, resistance to stressors, and injury recovery in childhood that may inhibit the onset or progression of specific adverse aging changes. Identification of such factors might ultimately lead to novel strategies for prevention of age-related conditions through the maintenance or restoration of such juvenile protective factors into adulthood. In 2007, NIA, in partnership with the Office of Dietary Supplements and the National Heart, Lung and Blood Institute, solicited research to identify and better understand these factors, resulting in eight awards. Grants awarded under these solicitations will be active in FY 2009.
- Conduct studies on nutrition, weight loss and maintenance, and exercise in the elderly. In FY 2007, NIA released solicitations for research grant proposals in a number of related areas, including studies of long-term weight maintenance, diet composition and energy balance, improving the measurement of diet and physical activity in clinical studies, and the role of nutrition in the prevention of common age-related conditions such as heart disease and cancer. Grants awarded under these solicitations will be active in FY 2009.
Intramural Research at NIA
NIA’s Intramural Research Program (IRP) includes the scientific disciplines of biochemistry, cell and molecular biology, structural biology, genetics, immunology, neurogenetics, behavioral sciences (psychology, cognition, and psychophysiology), epidemiology, statistics, and clinical research and the medical disciplines of neurobiology, immunology, endocrinology, cardiology, rheumatology, hematology, oncology, and gerontology. The program seeks to understand the changes associated with healthy aging and to define the criteria for evaluating when a change becomes pathologic. Studies focus on both common age-related diseases (e.g., Alzheimer’s disease, Parkinson’s disease, stroke, atherosclerosis, osteoarthritis, diabetes, cancer) and the determinants of healthy aging.
In FY 2009, the NIA IRP sustained a program of high-quality research on the basic biochemical and molecular underpinnings of aging and age-related diseases and conditions. In addition, IRP investigators conducted clinical research on a variety of conditions, including studies of the etiology of anemia, treatment trials for lymphoma, and studies to better understand several connective tissue disorders. In addition, work continued under the groundbreaking Baltimore Longitudinal Study of Aging, which will celebrate its fiftieth anniversary in 2008.
Budget Policy: The FY 2009 budget estimate for the NIA’s Intramural Research Program is $109,231,000, an increase of $1,614,000 or 1.5 percent over the FY 2008 level of $107,617,000. Additional funds will be used to partially offset the costs associated with pay raises and other increases. Program objectives for FY 2009 include plans to:
- Determine the effectiveness of already available therapeutic agents for prevention in models of heart disease. Animal studies suggest that the compound fenoterol, widely used for treatment of pulmonary disease, may be effective in the treatment of congestive heart failure. Other studies in animal models have shown that the drug erythropoietin, used to treat certain types of anemia, has a protective effect on the heart if administered shortly after a heart attack. Based on the results of these studies, NIA’s IRP initiated clinical trials in 2006 (erythropoietin) and 2007 (fenoterol) to establish the safety and efficacy of both agents in humans.
- Continue to study the effects of obesity and sarcopenia on health outcomes. The Health, Aging, and Body Composition (Health ABC) Study is an ongoing study of body composition and weight-related health conditions. Clinical examinations ended in 2007, and NIA has initiated five years of follow-up for physical and cognitive function, selected disease endpoints (fracture, heart disease, cancer, and stroke), cause-of-death assessment, and maintenance of the biorepository.
- Continue to study the driving factors behind persistent black-white health disparities in overall longevity, cardiovascular disease, and cerebrovascular disease. NIA is in the midst of data collection for its ground-breaking Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study. HANDLS is a community-based, epidemiological study evaluating health disparities in socioeconomically diverse African American and white populations located in Baltimore, Maryland. To date, the study has recruited half of the baseline cohort, so most research remains in a preliminary status with more complete analyses to be performed once the sample population is complete. However, several preliminary and ongoing analyses have produced interesting findings that support the value of this cohort as a unique resource. This 20-year research study, which began in 2004, will continue recruitment and data analysis during FY 2009.
- Identify genes associated with age-related changes to health and function. The aging process is governed by a range of biological pathways that have diverse effects across body systems and are not limited to specific diseases. Identifying gene variants associated with early disease onset, rates or aspects of age-related changes would provide vital insights into the aging process in humans and open up new areas for prevention, treatment, and prognostic testing. Ongoing studies include the SardiNIA Project, which is searching for genes associated with nearly 100 traits in a small, genetically homogeneous population; and the Age, Gene/Environment Susceptibility (AGES) Study, which is exploring genetic susceptibility and gene/environment interactions as these contribute to various health outcomes in old age. The AGES Study recently completed its baseline assessment of nearly 6,000 people and plans a five-year follow up that will permit one of most comprehensive descriptions of age-related changes in structure and function in multiple organ systems in an older population.
Program Portrait: Longitudinal Studies of Aging
The NIA supports longitudinal studies within both its intramural and extramural programs. These studies, in which data is collected repeatedly in groups of people over a period of months or years, can provide unique insights into the physiologic, health, economic, and other changes seen in populations over time. Data from longitudinal studies can be used to generate and test hypotheses about long-term effects of health exposures, factors affecting onset and progression of disease with advancing age, and protective factors that contribute to exceptionally healthy aging.
NIA supports America’s longest-running scientific study of human aging, the Baltimore Longitudinal Study of Aging (BLSA). Established in 1958, the BLSA has provided a wealth of information on the physical consequences of aging, as well as how to sort out changes due to aging from those due to disease, genetic makeup, environmental or lifestyle factors, or other causes. NIA is now planning to initiate the BLSA Elite Aging Study of men and women who have already achieved substantial longevity (85 years and older) and are still free of major diseases and disability. We anticipate that this study will provide critical information on the biological mechanisms that allow some people to substantially delay or even avoid age-related sickness and functional decline.
Another major NIA-supported longitudinal study, the National Long Term Care Study (NLTCS), fielded from 1982 to 2005, has been one of the leading resources for studying changes in health and functional status and for tracking health expenditures, Medicare service use, and the availability of personal, family and community resources for caregiving. No additional waves of data collection are currently planned
In recent years, a new generation of NIA-supported longitudinal studies has emerged. These new studies build on the ideas and hypotheses generated in earlier studies and therefore tend to focus on targeted specific aspects of aging and the aging process. For example, Health ABC is a study of age-associated changes in body composition and their effect on health and functional status in late life; the Women’s Health and Aging Study deals with risk factors for disability and disability progression in older women who are already impaired; investigators on the InCHIANTI study are collecting information on biomarkers of aging and are identifying factors affecting the development of mobility disability in late life; and the Health and Retirement Study focuses on the economic status of a cross section of the aging population in the United States. Other ongoing NIA-supported longitudinal studies include surveys focused on women’s health (for example, the Study of Women’s Health Across the Nation), cognitive health (e.g., the Nun Study), economic behavior and social and psychological measures (the Panel Study on Income Dynamics), and cardiovascular health (such as the Bogalusa Study).