FY 2018 Program Descriptions and Accomplishments
The primary goal of the NIA's Biology of Aging program is to improve our understanding of the basic biological mechanisms underlying the process of aging, which is the major risk factor for many chronic diseases and conditions affecting Americans. Basic biochemical, genetic, and physiological studies are carried out in both humans and animal models, including both mammals and non-mammalian organisms (e.g., flies, worms, yeast). The program also coordinates the NIH GeroScience Interest Group (GSIG), focused on identifying the molecular and cellular mechanisms that make aging the major risk factor for chronic diseases and disabilities. During FY 2018, the program will support research to increase our understanding of the changes in cellular architecture that occur during the aging process and the development of short-term tests that provide a comprehensive measure of resilience in animal models used in aging studies. In addition, this program will support research on AD, including studies of the influence of aging biology in all tissues and their effect on the nervous system and AD development and progression, including the role of the newly-identified brain lymphatic system on brain aging and health. The highly productive Interventions Testing Program to identify compounds that extend median and/or maximal life span in a mouse model is now in its second decade and will continue, along with a similar program to identify such compounds in the context of differing genetic backgrounds using the worm model Caenorhabditis. Finally, NIA Division of Aging Biology (DAB) -supported Nathan Shock Centers of Excellence in the Basic Biology of Aging have entered a third decade of providing state-of-the-art research resources to support basic aging research. This productive program will be renewed in FY 2017.
Program Portrait: Aging Biology and Geroscience at the NIA
Changes in cellular structure and function, whether naturally-occurring or induced or accelerated by exposure to environmental factors, are the major risk factor for many age-related diseases. The objective of research supported by the NIA Division of Aging Biology (DAB) is to increase our understanding of the basic biochemical, genetic, and physiological mechanisms underlying aging processes and age-related changes in both humans and model systems, with the ultimate goal of finding ways to increase the years of a healthy life, rather than just the lifespan.
During FY 2018, projects will be active under a suite of recent funding opportunity announcements (FOAs) soliciting basic research on Alzheimer's disease and related dementias. For example, one FOA is soliciting research on the interplay between the brain and other systems – immune, metabolic, organ-specific, or microbiome – that may influence the complex biology of AD. Another solicits research on the role of the brain's newly discovered "drainage system" – the glymphatic and lymphatic systems – in maintenance of brain health and development of disease.
An important focus within DAB is the emerging field of geroscience, which focuses on identification and understanding of the specific molecular and cellular mechanisms linking the aging process to chronic diseases and conditions. The trans-NIH GeroScience Interest Group (GSIG) was established in 2012, is led by NIA, and includes the participation of 22 Institutes within the NIH. GSIG-sponsored Geroscience Summits in October 2013 and April 2016 have generated influential publications in high-profile scientific journals. In 2013, the NIA also funded the Geroscience Network, a national interdisciplinary network of aging centers whose goal is to understand and exploit links between aging and chronic disease. In FY 2018, GSIG and Network investigators plan to continue research on effects of aging on disease and vice versa, and to identify promising interventional strategies with potential for testing in humans.
Behavioral and Social Research
NIA's Behavioral and Social Research Program supports research to understand and improve the processes of aging at the individual and population levels. Research areas include: 1) the behavioral, psychological, and social changes individuals experience over the adult lifespan; 2) participation of older people in the economy, families, and communities; 3) the development of interventions to improve the health, cognition, and well-being of older adults; and 4) the societal impact of population aging, including the effects of associated changes in labor force participation and socioeconomic circumstances on health. The program also supports: 1) development of publicly available, cross-nationally comparable datasets to facilitate research on the sources of international variations in health outcomes; 2) studies that integrate biology, including genetics, with social and behavioral science to elucidate the pathways by which social, psychological, economic, and behavioral factors affect health in middle age and late life; 3) longitudinal studies measuring behavioral and social variables that are relevant to health and change over the lifespan; 4) interventions to ameliorate the impact of disadvantage and reduce health disparities at older ages; 5) and interventions to improve well-being and maximize active life and health expectancy. The program coordinates the long-running Health and Retirement Study (HRS), the nation's leading source of combined data on health and socioeconomic circumstances of Americans over age 50. It also supports other longitudinal studies focusing on trends in late life disability (National Health and Aging Trends Study) and on the influences of behavioral, psychological, and social factors in midlife on age-related variations in health and well-being (Midlife in the United States Study). The program also coordinates the Centers on the Demography and Economics of Aging; the Edward R. Roybal Centers for Translational Research on Aging; and the Resource Centers for Minority Aging Research (RCMARs).
Major program activities that will be active in FY 2018 include initiatives to stimulate research on mid-life adults that can inform efforts to optimize health and well-being, prevent illness and disability in later years, and potentially reverse the negative impact of early life adversity on later life health. The program will sustain its research focus on Alzheimer's disease epidemiology, health disparities, and caregiving, and will also support research to improve quality of life for persons with Alzheimer's and related dementias at the end of life.
Geriatrics and Clinical Gerontology
As we age, our risk for many 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. This program also manages the NIA Clinical Research Study Investigator's Toolbox, a comprehensive resource containing templates, forms, guidelines, and related tools and information to support clinical investigators as they navigate an increasingly complex regulatory and research landscape.
The program also coordinates the Claude D. Pepper Older Americans Independence Centers Program, the goal of which is to increase scientific knowledge leading to better ways to maintain or restore independence in older persons. In addition, the program plans and administers clinical trials for a number of age-related conditions; for example, program-supported investigators are collaborating with the Patient-Centered Outcomes Research Institute (PCORI) on a clinical trial to test individually-tailored interventions to prevent fall-related injuries. Clinical trials of interventions to menopausal symptoms such as hot flashes; functional impairment in older individuals with HIV; and obesity in older Americans are ongoing and will be active in FY 2018. A current research focus, which will continue into FY 2018, is the study of behavioral interventions to address multiple chronic health conditions in primary care.
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 program's basic mission is to expand knowledge on the aging nervous system to allow improvement in the quality of life of older people. Ongoing activities include basic and clinical studies of normal brain aging as well as AD and related dementias and other neurodegenerative diseases of aging. These include molecular and cellular studies, animal models, genetics, drug discovery and development, diagnosis, clinical course, clinical trials for treatment and prevention of AD and other neurodegenerative diseases as well as for maintaining or improving cognitive health, sensory and motor function, and epidemiological studies to identify risk factors and establish prevalence and incidence estimates. NIA also supports a national network of Alzheimer's Disease Centers to translate research advances into improved diagnosis and care of patients, as well as implementing a broad array of studies aimed at improving our understanding of this disease.
Program Portrait: Biomarkers for Alzheimer's Disease and Related Dementias
Until perhaps 10 years ago, Alzheimer's disease could only be definitively diagnosed at autopsy. There was simply no reliable way to image AD's pathological hallmarks – beta-amyloid plaques and tangled threads of the tau protein – in living brain tissue, let alone to detect evidence of the disease in blood or cerebrospinal fluid (CSF). This lack of hard-and-fast physical diagnostic tools led to uncertainty among affected individuals. It also presented difficulties in treatment trials – many medical conditions can cause AD-like symptoms, but many of those conditions do not respond to treatments targeted at amyloid or tau. Researchers began to work toward the identification of biomarkers – biological signs that can be measured accurately and reproducibly, and that correlate with the absence, presence, progression, or regression of disease.
In 2004, NIH established the Alzheimer's Disease Neuroimaging Initiative (ADNI), a groundbreaking public-private partnership with the goal of identifying biomarkers for use in clinical trials. By 2009, ADNI investigators had revolutionized the field by establishing a method and standards for testing levels of beta-amyloid and tau in the CSF. They correlated levels of these proteins in the CSF with changes in cognition over time and determined that changes in these two protein levels in the CSF may precede the onset of the disease. This finding raised the possibility of using fluid and imaging biomarkers to track disease progression, as well as to assess rapidly the efficacy of interventions in clinical trials, and enabled a working group led by the NIA and the Alzheimer's Association to develop the first revisions to the clinical guidelines for Alzheimer's disease diagnosis in over 25 years. Today, ADNI Phase II continues to define changes in brain structure and function as people transition from normal cognitive aging to mild cognitive impairment to AD. A third phase, ADNI3, recently began recruitment and will build upon discoveries made in earlier phases through the use of innovative new measures and tools.
Other investigators are working to identify a range of biomarkers for AD and related dementias. For example, NIA-supported researchers are studying the use of a noninvasive imaging technique called optical coherence tomography to track subtle changes in the retina that may be associated with AD. Investigators are also exploring the use of blood-based biomarkers to diagnose AD, as well as structural changes to the brain associated with AD, brain glucose metabolism, and cerebral blood flow patterns. At this time, NIA is actively soliciting research studies to identify novel biomarkers to diagnose AD and to predict clinical course; projects funded as part of this initiative will be active in FY 2018.
As the lead federal agency for research on AD and related dementias, NIA leads implementation of research goals of the National Plan to Address Alzheimer's Disease. Recent initiatives have boosted support for research on AD and related dementias, including increases of $100 million in FY 2014, $25 million in FY 2015, and $350 million in FY 2016. The International Alzheimer's Disease Research Portfolio (IADRP), a publicly available database to capture the full spectrum of current AD research investments and resources throughout the world, continues to facilitate coordination of these efforts. Finally, NIA coordinates development of NIH's professional judgment budget for Alzheimer's disease. As mandated in the FY 2015 Appropriations Act, this document provides an estimate of additional funds needed to enable us to pursue fully scientific opportunities leading to a cure.1
Investigators with NIA's Intramural Research Program (IRP) conduct research in the areas of basic, behavioral, clinical, epidemiologic, and translational research. The main focus areas within the IRP are Neuroscience, Aging Biology, and Translational Gerontology. In state-of-the-art laboratories in Baltimore and Bethesda, Maryland, NIA IRP investigators work to understand 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 clinical research effort focuses on the translation of basic research findings, prevention, and therapeutic clinical trials focused on age-associated diseases, modulation of treatment efficacy and toxicity in older patients, and establishment of and maintenance of diverse longitudinal cohorts for aging research.
Many IRP studies focus on common age-related diseases such as AD, Parkinson's disease, stroke, atherosclerosis, and diabetes. Others, such as the groundbreaking Baltimore Longitudinal Study of Aging, explore the determinants of healthy aging and attempt to define the physiological measures of biological aging. 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 on the development of age-related health disparities among socioeconomically diverse African Americans and whites living in Baltimore.
Research Management and Support (RMS)
NIA's RMS activities provide administrative, budgetary, logistical, and scientific support in the review, award, and monitoring of research grants, training awards and research and development contracts. RMS functions also encompass strategic planning, coordination, and evaluation of the Institute's programs, regulatory compliance, international coordination, and liaison with other Federal agencies, Congress, and the public. The Institute currently oversees more than 1,736 research project grants and centers, as well as 500 full-time training positions and 72 research and support contracts.