NIA at Middle Age – Its Past, Present, and Future

Abstract

The National Institute on Aging at NIH leads the Federal effort conducting and supporting research on aging. It is also designated as the lead within NIH for research on Alzheimer’s disease. Since NIA’s establishment in 1974, the Institute has grown to a billion dollar enterprise, featuring a balanced program of basic, clinical, and behavioral and social science. Both investigator-initiated research and strategic investments have been critical to the NIA’s success in bringing new insights and understandings to aging processes and diseases and conditions associated with advancing age. In recent years, constraints in the growth of resources have posed new challenges, as the Institute and NIH leadership seek to maintain a robust and productive program. The authors will review the history of the NIA, discuss current programs and priorities, and point to new directions in research, looking ahead.

The National Institute on Aging (NIA), one of the 27 Institutes and Centers of the National Institutes of Health (NIH), leads the nation’s efforts to ensure that American elders enjoy a healthy, productive old age. The Institute’s mission—to discover what may contribute to a healthy old age as well as to understand and address the disease and disability sometimes associated with growing older—has never been more compelling. According to U.S. Census data, over 40 million people ages 65 and over lived in the United States in 2010. The baby boomers (born between 1946 and 1964) started turning 65 in 2011. By 2030, there will be some 72 million Americans ages 65 or older—more than double the number in that age group as compared with the year 2000. There are currently approximately 5.7 million of the “oldest old”—people age 85 or older—and this number is expected to more than triple between 2008 and 2050.¹

Since its establishment in 1974, the NIA has maintained a balanced program of basic, clinical, and behavioral and social science. With a 2012 budget of $1.1 billion, the NIA relies on both investigator-initiated research and strategic investments to generate new insights and understandings about aging processes as well as diseases and conditions associated with advancing age.

Early History

Research on aging has long been a priority for the NIH. In 1940, a $10,000 grant from the Josiah Macy Jr. Foundation facilitated the establishment of a Unit on Aging. A year later, the Unit on Aging moved from Bethesda, Maryland to Baltimore under the direction of noted gerontologist Nathan Shock, and by 1948 it was rechristened the Gerontology Branch and administratively moved to the National Heart Institute, where it would remain for the next 19 years.^2,3

Meanwhile, interest in aging was growing throughout the federal government. In 1956, the first Federal Council on Aging was convened, and a Special Staff on Aging was created within the Department of Health, Education, and Welfare. In 1961 the White House Conference on Aging, at the instigation of representatives of the Gerontological Society, recommended the formation of a National Institute of Gerontology.⁴ Finally, in 1974, Public Law 93-296 authorized the establishment of a National Institute on Aging and required that the Institute develop a comprehensive plan to coordinate the Health, Education, and Welfare agencies involved in aging research.

Understanding Aging in America

Among the NIA’s most significant contributions has been to define the parameters of “normal” aging. The Baltimore Longitudinal Study of Aging (BLSA) has been at the forefront of these efforts. The BLSA was established in 1958 to characterize normal aging and to distinguish changes due to aging from those due to disease or other causes, and its importance to the field of gerontology cannot be overstated.

Over the past 50 years, scientists have produced many notable findings based on BLSA data. For example, they found that depressed mood and affect is not a natural consequence of aging; indeed, personality remains relatively stable after age 30.^5,6 Other major BLSA findings include the discovery of the relationship between prostate-specific antigen levels and prostate cancer⁷ and between age-related changes in the arteries and cardiovascular disease.⁸ In recent years, the BLSA has adopted a new paradigm of functional aging incorporating several homeostatic networks and physiological domains, with mobility as primary outcome.⁹ In addition, the NIA has launched the IDEAL (Insight into the Determinants of Exceptional Aging and Longevity) study to identify the factors common to individuals whose lives are both very long and very healthy.

If the BLSA has laid a foundation of information about older Americans’ health, the groundbreaking Health and Retirement Study (HRS), launched in 1992, has provided considerable data about older Americans’ social and economic behaviors. Through unique, in-depth interviews with a nationally representative sample of adults over age 50, the HRS provides a growing body of multidisciplinary data on physical and mental health, insurance coverage, financial situations, family support systems, work status, and retirement planning. Linkage to administrative data on earnings and benefits from the Centers for Medicare and Medicaid Services and the Social Security Administration provide comprehensive information about lifetime earnings and benefits. More recently, the HRS has enhanced its measures of cognition, biomarkers, and physical performance, and in 2012 and 2013, 2.5 million single nucleotide polymorphism (SNP) genotyping for 20,000 HRS participants will be available to qualified researchers via the NIH Database of Genotypes and Phenotypes (dbGaP). Importantly, the HRS is a model for similar studies around the world, all making internationally comparable data freely available to researchers.¹⁰ Comparisons among these studies have yielded intriguing findings; for example, using data from the HRS and the English Longitudinal Study of Ageing, investigators found that Americans ages 55–64 are less healthy than their British counterparts across all socioeconomic groups, and that these findings cannot be attributed to biases in self-reporting or to behavioral risk factors including smoking, obesity, and alcohol use.¹¹

Helping Older People Remain Independent

As the aging population continues to grow, maintenance of functional independence at older ages remains a critical public health priority. The goal of the NIA’s Claude D. Pepper Older American Independence Centers program, established in 1991, is to increase scientific knowledge that will lead to better ways to maintain or restore independence to older persons. The NIA supports 13 Pepper Centers across the United States.

The Pepper Centers continue to generate findings with implications for clinical care. For example, a preliminary study demonstrated that older adults admitted to an Acute Care for Elders unit had a shorter length of stay when they increased their daily walking by at least 600 steps from the first to the second day of hospitalization.¹² An analysis of a randomized controlled trial of weight loss in older overweight or obese adults found that intentional weight loss resulted in lower mortality compared to subjects who did not have any weight loss; these data may allay some concerns that intentional weight loss in older overweight or obese adults is harmful.¹³

Studies have shown that regular physical activity can improve physical performance in older people, but definitive evidence that physical activity can prevent mobility disability is lacking. To address this gap, the NIA supports the Lifestyle Interventions and Independence for Elders (LIFE) Study, a phase III, multicenter randomized controlled trial to compare the effects of a structured physical activity program to a successful aging health education program in 1,600 sedentary older individuals. The primary study outcome is major mobility disability, defined as inability to walk 400 meters in 15 minutes, but the investigators are also assessing the intervention’s effects on cognition, falls, overall mortality and an array of other functional outcomes of importance to older individuals. The intervention’s cost-effectiveness will also be established.¹⁴ Completion of the study is anticipated in 2015.

Translating Basic Science into Clinical Practice

Ongoing attempts to identify potential interventional targets for age-related disease and disability come from research into the basic biology of aging, by searching for the intrinsic causes of aging. For example, the recent discovery that removal of senescent cells – which normally accumulate with age – delays the onset of aging-related dysfunctions opens new avenues for interventions to improve health in the elderly.¹⁵

Basic research in model organisms has also shown consistently that interventions extending lifespan can also increase the period of healthy life into older age. In 2003, the NIA established the Interventions Testing Program (ITP) to test agents and environments with the potential to extend lifespan and to rigorously evaluate potential therapeutics against functional declines, chronic illnesses and late-onset diseases that occur with aging.¹⁶ The ITP uses mice as a mammalian model of human aging. ITP investigators recently found that the immunosuppressant drug rapamycin extends lifespan in mice,¹⁷ and additional study is ongoing to further explore the drug’s impact on aging-related declines.

Over the years, findings from NIA’s clinical and translational research programs have had a significant impact on clinical care. For example, investigators on the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) found that people who are at high risk for diabetes can sharply reduce their risk by adopting dietary modifications and a moderate exercise regimen. This effect was most pronounced among participants age 60 and over. Treatment with the drug metformin (Glucophage®) also reduced diabetes risk among study participants, but for unknown reasons was less effective among older participants.¹⁸ A recently published DPPOS analysis indicates that prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years.¹⁹ DPP was the first major, randomized, multisite clinical trial to demonstrate that type 2 diabetes can be prevented or delayed in high-risk individuals, and the finding that exercise in particular is effective in preventing type 2 diabetes in older adults could have a tremendous public health impact.

The 12 Roybal Centers for Translational Research on Aging are supported by the NIA with co-funding from the NIH Office of Behavioral and Social Sciences Research and several other federal partners. These Centers are designed to move promising social and behavioral basic research findings into programs, tools, practices, and policies that will improve the lives of older adults and the ability of society to adapt to an aging population.

Roybal investigators have produced important findings in a number of arenas. One key area is older drivers. Age-related declines in driving ability are associated with a loss of independence and can be devastating to the older driver. NIA-supported investigators developed a test for useful field of view (UFOV)—the spatial area in which rapidly presented visual information can be processed and used.²⁰ Drivers who showed a 40 percent or greater impairment in their UFOV were more than twice as likely to be involved in a crash within three years of testing.²¹ The investigators went on to develop a training program to improve speed of processing (the rate at which an individual assimilates and acts on new information). This training has been shown to improve UFOV. Older drivers who completed speed of processing training made fewer dangerous maneuvers than did simulator-trained controls or a reference group during an on-road driving test.²² Today, this training is available through private companies, and in 2009, the AAA Foundation for Traffic Safety began to recommend one of these training programs to all AAA members.

Supporting Our Most Vulnerable Elders

Disparities in health status and medical care are most acutely experienced by the older population. Eliminating health disparities requires research that includes a special focus on the distribution of disease and disability between racial and ethnic groups in society.

Two important programs highlight NIA’s research emphasis in this area. The Resource Centers for Minority Aging Research (RCMAR) seek to help decrease health disparities by enhancing the diversity of the research work force, increasing the number of minority elders who participate in research studies, and developing culturally sensitive health measures and improved interventions to enhance health and well-being. RCMAR investigators have supported a number of important studies, including the first clinical trial of Sisters in Motion, a faith-based program to increase physical activity in older African American women; participation in the program was associated with increased physical activity and lower systolic blood pressure as compared to a control group.²³ The RCMARs also maintain a firm commitment to mentorship of diverse investigators. The Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study is a community-based, epidemiological study for evaluating health disparities in socioeconomically diverse African American and white populations in Baltimore. HANDLS investigators have recently found that racial discrimination is associated with red blood cell oxidative stress, suggesting a potential cellular pathway for health disparities in cardiovascular disease.²⁴ They have also identified loci associated with height²⁵ and renal function²⁶ among African Americans.

Alzheimer’s Disease: A Special Challenge, A Special Responsibility, A Special Opportunity

Alzheimer’s disease (AD) is a condition of particular interest to geriatricians, researchers, and patients. With between 2.4 million and 5.1 million Americans suffering with AD currently,²⁷ and these numbers anticipated to rise as the population ages, it has never been more urgent to develop new ways to prevent, manage, and cure AD.

Until 1976, little research had been conducted on AD and the research infrastructure was largely nonexistent.²⁸ Since then, NIA support has facilitated the development of a robust infrastructure for discovery, and in recent years our efforts have translated into important findings about AD with real-world implications for patients and people at risk.

In 1984, NIA established the AD Centers Program, exponentially expanding the field. Advances in the use of brain imaging came with the initiation of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in 2004 as a public-private partnership between NIH and other federal and private entities and the use of Pittsburgh Compound B (PiB) for the first time in 2004to image amyloid in brains of living persons.²⁹ In 2009, ADNI investigators established a method and standard of testing levels of tau and beta-amyloid proteins in the cerebrospinal fluid (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 signal the onset of AD.³⁰ These and additional research findings led, in 2011, to the development of new and more specific diagnostic criteria for the disease.

NIA also supports a robust portfolio of research on the identification and development of interventions to prevent, slow progression of, or cure AD. There are currently over 40 compounds under development through the Institute’s AD Translational Initiative, which supports studies that lead to the submission of an Investigational New Drug application to the Food and Drug Administration. Over 35 clinical trials, from small pilot studies to large-scale clinical trials, are also ongoing. In a recent, highly promising pilot trial, a nasal-spray form of insulin delayed memory loss and preserved cognition in people with cognitive deficits ranging from MCI to moderate AD.³¹ This finding, if confirmed in larger studies, could have a profound impact on the public health.

Importantly, the NIA has focused on the unique needs of Alzheimer’s disease caregivers. REACH (Resources for Enhancing Alzheimer’s Caregiver Health), an NIA-funded study, developed the first intensive caregiver support intervention to be proven effective, through rigorous testing, in an ethnically diverse population.³³ The REACH II protocol is a structured multicomponent intervention based on individualized assessment of caregiver needs. The REACH intervention is currently being translated more broadly through partnerships with the U.S Department of Veterans Affairs and the Administration on Aging.³⁴

Looking Ahead: Aging in the Twenty-First Century

In recent years, fiscal constraints have posed new challenges as the Institute and NIH leadership seek to maintain a robust and productive program. In response, NIA has taken several concrete steps to preserve the pay line and ensure continued advancement of the geriatrics field. For example, in early 2011, the Institute established a dual payline process involving separate paylines for Research Project Grants (RPGs) requesting $500,000 or more in annual direct costs and those requesting less than $500,000 in annual direct costs.

NIA has also exempted small grant applications (R03s) and exploratory/developmental applications (R21s) from consideration for the 18-percent administrative cut applied to other awards, and is continuing to give special consideration to applications from new and early-stage investigators. In addition, the NIA continues to seek and identify policies—for instance, encouragement of applications involving secondary analysis of data sets—to optimize existing resources. In these endeavors, program staff at NIA are supported by a comprehensive planning process in the development of a scientific portfolio consistent with the Institute’s strategic directions.³²

Despite recent challenges, NIA is moving ahead with a broad and comprehensive program of research aimed at improving the health of older Americans. For example, we will continue to pursue research in emerging fields such as behavioral economics, epigenomics, and systems biology while continuing to support established studies such as the BLSA and the HRS. In addition, a proposed Obama Administration initiative will – if fully implemented – invigorate the research enterprise with an infusion of funds for research, caregiver support, provider education, public awareness, and improvements in data infrastructure.

As the NIA approaches its own middle age, the future looks bright. We will continue to take advantage of scientific opportunities while supporting investigators in aging research. Our continued investment in the lives and health of older Americans remains critical to older people and to the nation.