Justification Narrative

• Director's Overview
• Overall Budget Policy
• Narrative by Program
  
  • Biology of Aging Program
  • Behavioral and Social Research Program
  • Neuroscience and Neuropsychology of Aging
  • Program Portrait: Alzheimer's Disease Research
  • Geriatrics and Clinical Gerontology Program
• Intramural Research at NIA
• Research Management Support

Authorizing Legislation: Section 301 and title IV of the Public Health Service Act, as amended.

Budget Authority:

This document provides justification for the Fiscal Year (FY) 2008 activities of the National Institute on Aging (NIA), including NIH/AIDS activities. Details of the FY 2008 HIV/AIDS activities are in the "Office of AIDS Research (OAR)" section of the Overview. Details on the Roadmap/Common Fund are located in the Overview, Volume One.

Director's Overview

There are currently 35 million Americans over the age of 65. Of these, more than four million are over 85, and some 65,000 have attained their hundredth birthday. By 2030, the number of individuals age 65 and older will likely double, reaching 70.3 million and comprising a larger proportion of the entire population, rising from 13 percent today to 20 percent in 2030, and the number of the "oldest old" -- people age 85 and older -- is expected to grow from 4.3 million in 2000 to at least 19.4 million by 2050. 1

As life expectancy increases, we are challenged to find ways to keep the additional years of life free of disease and disability. Today, more than half of all Americans over age 65 show evidence of osteoarthritis in at least one joint.2 Over half of Americans older than 50 have osteoporosis or low bone mass.3 Cardiovascular disease, cancer, and diabetes remain common among older Americans, and as many as 4.5 million Americans suffer from Alzheimer's disease (AD).4 For many, modern medicine and new insights into lifestyle and other environmental influences are allowing people to remain healthy and socially and emotionally vital into very advanced ages; however, NIA supported research continues to address the needs of the growing number of people who will live longer.

The National Institute on Aging (NIA) leads a national scientific effort to understand the nature of aging and to extend the healthy, active years of life for all Americans. NIA achieves its mission through a robust extramural research program composed of the four research areas as described in the Budget Justification section plus a vibrant intramural research program.

NIA's research programs cover a wide range of topics critical to understanding aging and its interaction with the initiation and progression of disease and disability. For example, NIA research has identified lifestyle factors and health behaviors that directly influence physical and mental fitness and risk of disease in aging populations. NIA-supported scientists develop and refine recommendations for people of all ages regarding optimal diet, dietary supplement use, exercise, and safety to increase their likelihood of enjoying a physically and mentally healthy old age. Other researchers work to find better ways to enhance the physical, mental, and interpersonal capabilities of older people and to expand opportunities for them to achieve personal goals and contribute to society in meaningful ways. Still others explore the molecular, cellular, and genetic changes that take place in the body as we age, with the ultimate goal of developing new prevention strategies and novel therapeutic approaches to eliminate or delay the debilitating physical, cognitive, and psychological changes that can occur.

As the research on aging advances, NIA will focus more effort on the translation of basic research findings into clinical studies and trials. The institute supports large multidisciplinary programs in translational research, including:

• Edward R. Roybal Centers for Research on Applied Gerontology, designed to advance promising social and behavioral basic research findings from the laboratory and into programs, practices, and policies to improve the lives of older people and enhance the capacity of the nation to adapt to the societal shifts that come with an aging population.
• Claude D. Pepper Older American Independence Centers (OAIC), established to increase scientific knowledge for the development of innovative and cost-effective ways to maintain and restore independence.
• The Alzheimer's Disease Translational Initiative, a major effort to encourage more researchers to move from basic research on Alzheimer's disease and associated disorders into translational research and drug testing in clinical trials. Components of this initiative include program announcements on drug discovery and preclinical development and a program of toxicology services for academic and small business investigators who believe they have promising compounds for the treatment or prevention of Alzheimer's disease but lack the resources to perform the required toxicology studies.

Additional translational research efforts include:

• Recent findings which have shown that overweight, aged male mice whose high-calorie diet was supplemented with the natural compound resveratrol had better health and longer survival than their counterparts who did not receive it. NIA plans to test the effects of dietary supplementation with resveratrol in non-human primates, an important step to inform the consideration of human clinical trials.
• Several studies which suggest that physical exercise may prevent physical disability, including impaired mobility, in healthy and frail older adults. To develop definitive evidence, NIA and grantee researchers have developed the LIFE (Lifestyle Interventions and Independence in Elders) study, a clinical trial testing the effects of a physical activity program vs. a health education program among older Americans. A successful pilot study (LIFE-P) completed in 2005 showed both feasibility and positive preliminary data, permitting design and consideration of this large-scale clinical trial.
• A large body of research in animal models which indicates that substantially reducing caloric intake while maintaining optimal nutrition results in significant increase in life span. NIA-supported Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) will help to determine if these beneficial effects extend to humans. Results from pilot studies demonstrated that overweight people who cut their calories by 25 percent for six months have reduced fasting insulin levels and core body temperature, two markers that may be associated with increased longevity in humans. A longer-term study will begin in January 2007.

NIA's Intramural Research Program is very active in the translation of basic research findings to clinical studies. One of its primary resources, the Advanced Studies in Translational Research on Aging (ASTRA) unit, is a state-of-the-art facility located at Baltimore's Harbor Hospital. ASTRA, opened in January 2003, is equipped with a fully functional 10-bed acute care inpatient unit, an outpatient examination and treatment unit, and other resources vital to the conduct of translational research. Recently, the Baltimore Longitudinal Study of Aging, which has been the gold-standard reference for all epidemiological studies on aging, was moved to the ASTRA unit where NIA plans to launch a number of ancillary studies that are more likely to provide information that can be directly applied to clinical medicine.

Overall Budget Policy

Investigator-initiated research projects and new investigator research and career development are the Institute's highest priorities. In order to maximize the number of competing research project grants that can be made, NIA has a cap on the amount that can be awarded to individual program project awards and is following the NIH policy in providing no inflationary increases for non-competing or competing grants. In addition, the NIA has targeted a portion of the funds available for competing research project grants to support high priority projects outside of the payline, including awards to new investigators and first-time renewals. The Institute also seeks to maintain a balance between solicitations issued to the extramural community in areas that need stimulation and funding made available to support investigator-initiated projects.

Narrative by Program

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 biochemical, genetic, and physiological mechanisms that underlie the process of aging and age-related changes in humans and in animal models. BAP supports research on age-related changes in structure and function, from the molecular and cellular level to entire organisms, as well as the ways in which these changes are related to diseases and conditions common to aging. This program supports integrated research on genetics and other aspects of aging-related changes in multiple model systems, including both mammals and non-mammalian organisms (e.g. flies, worms, and yeast).

Budget Policy: The 2008 budget estimate for the Biology of Aging Program is $175,672,000, an increase of $72,000 or 0.04 percent from the FY 2007 Continuing Resolution of $175,600,000. Program objectives for FY 2008 include plans to:

• Continue the search for interventions that extend the lifespan. The recent finding that resveratrol could affect the health and survival of mammals exemplifies the promise of this research. An important component in this area is the Intervention Testing Program, which supports the testing of compounds with the potential to extend the lifespan and delay disease and dysfunction in a mouse model. Plans are to renew this promising initiative in FY 2007 for funding in FY 2008.
• Continue to search for genes and biological pathways that influence longevity and aging. NIA's primary mechanism for this endeavor is the Longevity Associated Gene initiative, which to date has identified over one hundred new longevity-associated genes, along with many conserved biological processes and pathways that regulate longevity in a host of divergent species, including humans.
• 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.
• Understand the role of nuclear receptors in aging. Research supported under two complementary program announcements will focus on the biologic mechanisms that underlie the activity of nuclear receptors, which are molecules that play key roles in various physiologic and pathophysiologic processes, including those involved in aging and in age-related diseases.
• Continue the highly successful Nathan Shock Centers of Excellence in Basic Biology of Aging. These centers enhance the ability of institutions with well-developed research programs in basic research on aging to use state-of-the-art research resources to provide the strongest environment for the conduct of research on aging.

Behavioral and Social Research Program:
Understanding and Addressing the Behavioral, Emotional, and Social Dynamics of Aging

NIA 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, and a knowledge base for the development of interventions to maximize active life and health expectancy.

Budget Policy: The 2008 budget estimate for the Behavioral and Social Research Program is $168,850,000, an increase of $70,000 or 0.04 percent from the FY 2007 Continuing Resolution of $168,780,000. Program plans for FY 2008 are to:

• Initiate a new wave of the National Long-Term Care Survey (NLTCS) and continue other major demographic studies. The NLTCS is a longitudinal survey to study changes in the health and functional status of older Americans and track health expenditures; Medicare services used; and the availability of personal, family, and community resources for caregiving. It is considered one of the most useful resources for analyzing national disability trends. Other important ongoing studies include the Health and Retirement Survey and collaborations with the Census Bureau and the Federal Forum on Aging.
• Support research initiatives to address financial challenges faced by American elders. Funding for two major initiatives in this area will run through FY 2008. One initiative, "Developing Integrated Economic Models of Health Retirement," will stimulate 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 research on ways in which data from ongoing clinical trials and other studies can be used to plan and prepare for future natural and man-made disasters. Three coordinated research solicitations focused on behavioral and social aspects of disasters were released in 2006 to stimulate research on the consequences of natural and man-made disasters and their effects on the health of vulnerable groups, with the ultimate goal of preventing and/or mitigating harmful consequences.

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 neurologic disorders associated with aging.

Budget Policy: The 2008 budget estimate for Neuroscience and Neuropsychology of Aging Program is $413,131,000, an increase of $171,000 or 0.04 percent from the FY 2007 Continuing Resolution of $412,960,000. Program plans for FY 2008 are 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 disease's molecular underpinnings to cutting-edge diagnostic and treatment modalities. NIA will continue a comprehensive drug development program and pilot trials initiative 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. (See the "program portrait.")
• Support research on maintenance of cognitive and emotional health into older age. NIA joined with the National Institute of Mental Health and the National Institute on Neurological Disorders and Stroke to launch the Cognitive and Emotional Health Project, which is designed to assess the state of longitudinal and epidemiological research on demographic, social, and biologic determinants of cognitive and emotional health in aging adults and the pathways by which cognitive and emotional health may reciprocally influence each other. A "Cognitive Health Summit" planned for Spring 2007 will inform future research in this area.
• Develop new tools, resources, and training opportunities to accelerate the pace of discovery in neuroscience research through participation in the NIH Blueprint for Neuroscience Research. NIA is one of fifteen NIH Institutes that participate in the Blueprint, designed to enhance collaboration through coordinated initiatives. The first Blueprint initiatives began in FY 2005. The priority in FY 2007 is neurodegeneration with neurodevelopment the priority in FY 2008.
• 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 researchers recently identified a misfolded protein that is common to FTD and ALS, which provides important insights about the mechanisms of both diseases.

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.

Budget Policy: The 2008 budget estimate for the Geriatrics and Clinical Gerontology Program is $135,148,000, an increase of $55,000 or 0.04 percent from the FY 2007 Continuing Resolution of $135,093,000. Program objectives for FY 2008 include plans to:

• Initiate studies of venous and arterial thrombosis in the elderly. Advanced 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 will explore the biological mechanisms, epidemiology, pathophysiology, and clinical aspects (diagnosis, treatment, and prevention) of this common condition.
• Continue clinical trials of the efficacy and safety of testosterone in older men for a variety of conditions. Two trials are targeted to begin in mid-2007 -- one for men over 65 and one for younger men. The trials are expected to run for approximately six years. Participants will include men who are experiencing clinical symptoms related to low testosterone levels. Although these are treatment studies, the results may inform future prevention trials.
• Continue research on anemia in the elderly. Anemia is common among older people; however, over half the 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. Findings from this research may prove critical to the development of clinical trials.

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 2008, NIA's IRP will celebrate the 50th anniversary of the Baltimore Longitudinal Study of Aging, America's longest-running scientific study of human aging. More than 1,400 men and women, ranging in age from the 20s to the 90s, have been study volunteers. Since its inception in 1958, the BLSA has generated numerous findings to elucidate the normal course of aging and disentangle the effects of disease from the normal aging process.

Budget Policy: The 2008 budget estimate for NIA's Intramural Research Program is $101,370,000, a decrease of $710,000 or 0.7 percent from the FY 2007 Continuing Resolution of $102,080,000. Program objectives for FY 2008 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. NIA's IRP is conducting preclinical testing of both agents with the goal of moving them into human clinical trials in future years.
• 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 will end in 2007, at which time NIA plans to initiate five years of focused event 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 for evaluating health disparities in socioeconomically diverse African American and white populations in Baltimore, Maryland.

Research Management Support

NIA 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 1,840 research project grants and centers, as well as more than 500 full-time training positions and 100 research and support contracts.

Budget Policy: The 2008 budget estimate for NIA's Research Management and Support is $39,194,000, an increase of $388,000 or 1.0 percent over the FY 2007 Continuing Resolution of $38,806,000. Additional funds will be used to partially offset the costs associated with pay raises and other mandatory increases.