Biology of Aging Program:
Understanding Aging Processes, Health, and Longevity
Investigators supported by NIA’s Biology of Aging Program 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, yeast). The program’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.
Budget Policy: The FY 2011 budget estimate for the Biology of Aging Program is $174.131 million, an increase of $4.762 million or 2.8 percent over the FY 2010 estimate. Ongoing initiatives that will remain active during FY11 include the Interventions Testing Program to identify compounds that extend median and/or maximal life span in a mouse model; an initiative to develop tools needed to determine cell fates in various tissues of aged mammals, both under normal and injury conditions; and a joint effort with the National Institute of Allergy and Infectious Diseases to understand and remediate age-related decline in the immune system. Also, a recent initiative has funded six collaborative projects between US and British investigators interested in different aspects of the biology of aging. The program also coordinates the Nathan Shock Centers of Excellence in the Basic Biology of Aging; renewal of the Shock Centers is anticipated for FY2010.
Behavioral and Social Research Program:
Understanding and Addressing the Behavioral, Emotional, and Social Dynamics of Aging
NIA’s Behavioral and Social Research Program supports social and behavioral research to better understand the processes of aging at the individual, institutional, and societal levels. Research areas include the behavioral, psychological, and social changes individuals undergo throughout the adult lifespan; participation of older people in the economy, families, and communities; the development of interventions to improve the health and cognition of older adults, and the societal impact of population aging and of trends in labor force participation, including fiscal effects on the Medicare and Social Security programs. The program also supports research training; development of research resources such as publicly available, cross-nationally comparable studies that support research to understand the sources of international variations in health outcomes; interdisciplinary studies that integrate biological and genetic measures with traditional social, behavioral and economic measures; and a knowledge base of longitudinal databases for the development of interventions to maximize active life and health expectancy. These activities will remain active through FY 2011. The program coordinates the Centers on the Demography and Economics of Aging and Roybal Centers for Translational Research on Aging, as well as the Resource Centers for Minority Aging Research (RCMARs). The RCMAR program’s objectives include increasing the diversity of the scientific workforce studying aging and developing recruitment and retention strategies for minority aging research.
Budget Policy: The FY 2011 budget estimate for the Behavioral and Social Research Program is $188.063 million, an increase of $5.143 million or 2.8 percent over the FY 2010 estimate. This program will be expanded to more fully address its research objectives and more quickly translate NIA research into benefit for aging Americans and the nation as a whole.
Understanding, Preventing, and Treating Cognitive Decline and Disability
NIA’s Neuroscience 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 aging 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 problems arising from psychiatric and neurological disorders associated with aging. An emerging focus is on how the process of aging and age-related cognitive decline intersect with the development of Alzheimer’s disease and other dementias of aging.
Budget Policy: The FY 2011 budget estimate for the Neuroscience Program is $477.729 million, an increase of $13.064 million or 2.8 percent over the FY 2010 estimate. This program will expand support for a broad spectrum of basic, clinical, and translational research related to the pathology, prevention, diagnosis, treatment, and care of Alzheimer’s disease; a major activity planned for FY2011 is the renewal of the highly successful Alzheimer’s Disease Neuroimaging Initiative. The funds requested will allow for an expansion to more fully address its research objectives and more quickly translate NIA research into benefit for aging Americans.
Program Portrait: NeuroimagingFY 2010 level: $80,200,000
FY 2011 level: $82,500,000
Researchers and clinicians use today’s safe, painless, noninvasive neuroimaging techniques – including positron emission tomography (PET) and magnetic resonance imaging (MRI) – to diagnose brain injury or disorders, monitor the treatment of people with neurological disease, and learn more about the inner workings of the brain in normal and disease states.
One exciting area of neuroimaging research is the use of PET, MRI, and similar tools to understand and diagnose Alzheimer’s disease (AD). Bolstered by the development of new tracers such as Pittsburgh Compound B, which permits for the first time visualization of AD’s hallmark amyloid plaques in the living brain, investigators have made tremendous inroads in this area. The cornerstone of NIA’s AD neuroimaging program is the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a major public-private partnership among NIH and academic and industry partners through the Foundation for NIH. ADNI’s overall goal is to identify the best imaging biomarkers or combinations of imaging and molecular biomarkers for monitoring disease progression and treatment response. Since its inception in 2004, this study has made important progress; notably, ADNI investigators have established a method and standard for measuring levels of two known AD biomarkers in the cerebrospinal fluid, and determined that changes in these levels may signal the onset of mild AD. This is a significant step forward in developing a diagnostic test for AD. Funding provided under the American Recovery and Reinvestment Act expands the scope of the original ADNI research by allowing the enrollment of participants at an even earlier stage of mild cognitive impairment (often a precursor condition to AD). Clinical, imaging, and biological data from ADNI are immediately made available to all qualified scientific investigators in the public and private sectors, whether they are part of the study or not. Already, many of the tools and methods developed by the study are fueling similar efforts in Japan, the European Union, and Australia. This groundbreaking program will be active through FY2010 and is slated for potential renewal in FY2011.
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 Program supports research on health, disease, and disability in the aged (other than neurodegeneration, which is the focus of the NIA’s Neuroscience 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. Program staff work closely with other NIH Institutes to coordinate research on diseases and conditions that are common among older people (for example, a long-term partnership with NCI encourages coordination of aging and cancer research) or represent a growing threat (for example, an ongoing collaboration with NIAID addresses the increasing incidence of HIV/AIDS among older Americans). The program also plans and administers clinical trials for a number of age-related conditions. In addition, the program coordinates 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.
Budget Policy: The FY 2011 budget estimate for the Geriatrics and Clinical Gerontology Program is $143.243 million, an increase of $3.917 million or 2.8 percent over the FY 2010 estimate. Research of the Geriatrics and Clinical Gerontology Program will be expanded to more fully address its research objectives and more quickly translate NIA research into benefit for aging Americans and the nation as a whole.
Program Portrait: OsteoporosisFY 2010 level: $40,000,000
FY 2011 level: $41,200,000
It is estimated that 10 million men and women in the United States currently have osteoporosis and an additional 34 million have low bone mass and are at risk. In fact, one of every two women and one in four men over age 50 will have an osteoporosis-related fracture in his or her lifetime. NIA supports an extensive portfolio of research on the epidemiology, causes, and treatment of this common condition.
NIA partners with the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support two long-term epidemiologic efforts focused on fracture risk in women and men, the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men study (Mr. OS). Both of these studies have provided important information about potential risk factors for osteoporosis. For example, recent findings from these studies indicate that use of commonly prescribed antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) is associated with reductions in bone mineral density among men and an increased rate of bone loss at the hip in women. Because bone loss is common among older people, the finding that SSRIs may be a significant contributing factor to osteoporosis could have significant public health implications.
Findings from basic research suggest that bone mass is regulated through a complex interaction of hormones and other factors throughout the body, not exclusively in the bone. Researchers have found that the hormone leptin, which is secreted by fat cells, regulates bone mass through a central relay involving the brain’s serotonin system. This finding has generated considerable interest and raised many additional questions about how activity in the brain influences skeletal physiology, and about the potential involvement of other proteins, hormones, and neurotransmitters in regulating bone mass. Notably, investigators recently found that the protein Lrp5, which is heavily involved in regulation of bone mass, acts not directly through the bone, as was previously believed, but rather via serotonin synthesis in the gut. The central regulation of bone mass was the topic of an NIA workshop in June 2009, and will be an important research focus in the immediate future.
Other NIA-supported osteoporosis research includes the Study of Women’s Health Across the Nation (SWAN), which is examining changes in bone mass, bone turnover, and bone strength in a multiethnic (Chinese, Japanese, African American and Caucasian) cohort as the participants age. NIA also supports a number of projects on dietary and other interventions to prevent or treat osteoporosis and osteoporosis-related fractures in older men and women.
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. Some NIA IRP studies focus on common age-related diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, atherosclerosis, osteoarthritis, diabetes, and cancer. Others, such as the groundbreaking Baltimore Longitudinal Study of Aging explore the determinants of healthy aging. Ongoing NIA IRP research includes studies of the etiology of anemia, treatment trials for lymphoma, and studies to better understand several connective tissue disorders, as well as basic research on the pathology of Alzheimer’s disease, Parkinson’s disease, and other neurological conditions. Work is also continuing on the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, which is examining the influences of race and socioeconomic status (SES) on the development of age-related health disparities among socioeconomically diverse African Americans and whites living in Baltimore.
Budget Policy: The FY 2011 budget estimate for the NIA’s Intramural Research Program is $116.101 million, an increase of $3.6 million or 3.2 percent over the FY 2010 estimate. Funds requested will be used to expand efforts in understanding the genetics of neurological disease, as well as improving NIA’s capital equipments stock and other activities.
Program Portrait: Genetics of Neurological DiseaseFY 2010 level: $68,200,000
FY 2011 level: $70,200,000
Identification of the genes or specific genetic alterations involved in the development and progression of disease can help us identify people at risk, provide important insights into the disease’s pathology, or even suggest targets for a preventive or treatment intervention. We can also use information about disease-related genes to create models in which to test potential preventive or treatment interventions.
NIA conducts and supports an extensive program of research to identify genes implicated in neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. Until recently, only four genes had been definitively associated with AD, and three of these are exclusively associated with the rare early-onset form of the disease. In recent studies of the whole genome, investigators found three additional genes that, when altered, may be associated with increased risk of late onset disease; these researchers also identified several additional genes that merit further investigation. In 2009, NIA funded the Alzheimer’s Disease Genetics Consortium (ADGC) to collaboratively use the collective resources of the AD research community to identify additional risk factor genes for late-onset AD. NIA has also established the Dominantly Inherited Alzheimer Network to better understand the onset and development of early-onset AD by identifying concurrent changes in imaging and other biomarkers, as well as in cognitive and clinical symptoms. Better understanding this form of the disease may provide clues to decoding other dementias and developing dementia tests and treatments.
NIA also maintains a Laboratory of Neurogenetics (LNG) within its Intramural Research Program. The LNG’s mission is to find the genes and gene mutations that cause or contribute to neurological disease. The primary disease focus in the LNG is PD, but research is also ongoing in amyotrophic lateral sclerosis, dementia, dystonia, ataxia, and stroke. LNG investigators were responsible for the groundbreaking discovery that triplication of the synuclein gene causes some forms of PD; shortly thereafter, investigators identified the most common genetic cause of PD, mutations in LRRK2, which are believed to underlie about 20,000 cases of PD in the United States today. LNG research has also uncovered genes for such rare conditions as spinocerebellar ataxia 15 (SCA15), SCA11, SCA20 and dystonia-parkinsonism 16. Most recently, LNG scientists have completed a large collaborative study, the first of its kind, to identify common genetic risk factors for PD. They were also collaborators in one of the partnerships that recently identified additional risk factor genes for late onset AD.