Director's Statement

Mr. Chairman and Members of the Committee:

I am pleased to present the President’s budget request for the National Institute on Aging (NIA) for FY 2002, a sum of $879,961,000, which reflects an increase of $93,509,000 over the comparable Fiscal Year 2001 appropriation. The NIH budget request includes the performance information required by the Government Performance and Results Act (GPRA) of 1993. Prominent in the performance data is NIH's second annual performance report which compares our FY 2000 results to the goals in our FY 2000 performance plan. As performance trends on research outcomes emerge, the GPRA data will help NIH to identify strategies and objectives to continuously improve its programs.

Evidence suggests that older Americans are living longer, healthier lives. Life expectancy in the United States has dramatically improved from an average of 49 years in 1900 to 76 years at the turn of the 21st century.* The results of several national surveys also suggest that older Americans are experiencing better health and a declining rate of disability. Despite this promising news, we know that good health is not a universal reality for all older Americans—especially for aging minority groups. Thus, the NIA is committed to supporting high quality research to address the conditions and diseases affecting the elderly population, such as Alzheimer’s disease (AD), osteoporosis, cardiovascular disease, cancer, diabetes, and physical frailty.

AD, the most common cause of dementia among older persons, tragically affects as many as four million Americans who are predominately 65 years and older. There has been an explosion of recent findings that are yielding important clues about AD risk factors and disease pathology and, as a result, are suggesting targets for treatment and prevention.

In the past year, scientists have identified a number of genetic and non-genetic AD risk factors. Separate studies concluded that a gene or genes on chromosome 10 may be risk factors for late onset AD—the most common form of AD. Prior to these findings, the apolipoprotein E (APOE) gene was the only widely recognized genetic risk factor in late onset AD. Examples of possible non-genetic risk factors uncovered recently include poor socioeconomic status, low-educational level, absence of extensive social networks, and history of serious head trauma. Evidence from these and other studies suggests that early life course events may play a role in AD development and could lead to novel interventions.

While research is ongoing to explain how AD develops, scientists are also working to translate information about risk factors and underlying disease mechanisms into effective AD treatments. The public and scientific community are particularly excited about an emerging, potentially promising AD vaccine. In a breakthrough experiment last year, which was based upon NIH-supported advances in basic research, pharmaceutical company scientists announced they had developed a vaccine that in mice appears to slow production of amyloid. Amyloid is the substance, or peptide, that forms the senile plaques in the brains of AD patients. Their research showed that repeated long-term injections of an amyloid vaccine can stimulate an immune response in test mice, nearly eliminating amyloid plaques and associated neuropathology. (Chart #1) A number of NIH-funded scientists have since confirmed and extended these observations. Other NIA-supported studies have shown that the vaccine is effective in preventing cognitive decline in mice. Human trials being conducted by pharmaceutical company researchers are now beginning to test both the safety and efficacy of these vaccines as a possible therapy for AD. The NIA is discussing potential ways in which the public and private sectors can collaborate to facilitate the success of these critical trials.

The NIA is currently supporting 17 AD clinical trials, seven of which are large-scale cognitive impairment and AD prevention trials. These trials are testing agents, such as estrogen, anti-inflammatory drugs, and anti-oxidants, for their effects on slowing progress of the disease, delaying AD’s onset, or preventing the disease altogether. Other intervention trials being supported by the Institute are assessing the effects of various compounds on the behavioral symptoms (agitation, aggression and sleep disorders) in people with AD. The NIA is also supporting studies that are testing interventions for improving AD patient care delivery and alleviating caregiver burden.

Besides AD, many other chronic diseases and disabling conditions can compromise the quality of life for older people. Osteoporosis, a skeletal disorder characterized by compromised bone strength, is one of the seven most common causes of disability in older people, especially older women. According to the National Institute of Arthritis and Musuloskeletal and Skin Diseases, one out of every two women (as opposed to one in eight men) over 50 will have an osteoporosis-related fracture in her lifetime. Large observational studies have determined that the use of thiazide diuretics, an inexpensive treatment for high blood pressure, is associated with higher bone density and about a 30% lower risk of hip fracture. To directly test the effects of low-dose hydrochlorothiazide on bone density in men and women with normal blood pressure, investigators completed a recent clinical trial. The trial found that the agent preserved bone density at the hip and spine. The modest effects observed over three years, if accumulated over 10–20 years, may explain the 30% reduction in hip fracture risk associated with thiazides in the earlier observational studies. The results of this trial suggest that low-dose thiazide therapy may have a role in preventing osteoporosis.

Diabetes is another one of the seven major debilitating diseases affecting older people. Adult onset diabetes, or type 2 diabetes mellitus (DM), is caused by an inability of the beta cellsof the pancreas to compensate for increasing insulin demands; consequently, blood glucose levels rise. GLP-1, a glucagon-like gut peptide, can stimulate beta cells to produce more insulin even in type 2 DM; however, its biologic half-life is short and its effects quickly diminish. Exendin-4, a newly studied peptide analog of GLP-1, is long-lived and more potent than GLP-1, and has been shown to reduce blood glucose levels in rodents. A recent study with small numbers of diabetic and non-diabetic humans demonstrated Exendin-4’s efficacy in inducing insulin and normalizing blood sugar, even in diabetics. (Chart #2) In the near future, an exendin-like drug possibly may become an effective treatment for type 2 DM.

Research has shown that many of the disabling conditions affecting older people could be diminished through regular exercise. The evidence was enhanced this year by findings that found fitness affects mortality risk regardless of an individual’s body fat. One study, which followed men 30-83 years of age for an average of eight years, found that within each category of body fatness,“fit” men (as measured by exercise testing) were at a lower risk of death. In addition, among fit men, obesity was not significantly related to risk of death. In another study, low fitness increased mortality risk in men approximately fivefold for cardiovascular disease and threefold for all-cause mortality. Low fitness was associated with higher mortality in all weight groups. Findings like these motivate the NIA to continue its ongoing campaign to encourage older people to exercise. Since the campaign was launched in 1998, the NIA has distributed over 350,000 copies of its exercise guide and over 15,000 copies of its companion video to the public.

In keeping with its mission, the NIA supports research on diseases and conditions affecting the elderly as well as on the normal aging process. To understand the aging process, it is important to identify those factors that affect the overall life span of an organism. Toward this end, NIA supports and promotes research on the biochemical, genetic, and physiologicalmechanisms of aging and the onset of age-related disease. Experiments in a number of animal models, such as mice, fruit flies, and nematodes (roundworms), are providing valuable insights.

Understanding factors that contribute to longevity in animal models, and how these factors may apply to humans, are of major interest to the NIA. The role that oxidative stress, for example, may play in the aging process continues to be explored. In the last year, investigators announced that they had extended the average life span of nematodes via pharmacological intervention targeting oxidative stress. Using an artificial compound, EUK-134, which mimics enzymes that reduce oxidative damage, researchers extended the life span of nematodes by about 50%. The intervention also reversed premature aging in a nematode strain subject to elevated damage. These results strongly suggest that oxidative stress is a major factor in the rate of aging in the nematode and may be slowed by pharmacological intervention. It may be that similar compounds could lessen oxidative stress in humans and delay or reduce age-related pathology.

Caloric restriction, which entails a diet that includes all of the necessary nutrients but fewer calories, has been shown to slow the intrinsic rate of aging and to delay and reduce the onset of diseases, such as cancer. In rodents, it was demonstrated recently that caloric restriction can also increase resistance of neurons to age-related and disease-specific stresses, suggesting that it may be an effective approach for reducing neuronal damage and neurodegenerative disorders in aging. Although the effects of caloric restriction on humans have not been evaluated, this year, the NIA announced an initiative to begin studying the effects in humans of sustained caloric restriction on physiology, metabolism, body composition, risk factors for age-related pathologies, progression of age-related changes (where feasible), and its potential adverse effects. Results of these studies could be valuable in the development of better methods of preventing multiple age-related diseases.

Behavioral and lifestyle factors have a profound impact on health throughout the life span. Thus, the NIA supports behavioral and social research, including demographic research, to elicit information about the health of older people, their socioeconomic status and the social and behavioral influences that affect their lives.

Demographers reported some of the most promising news of the last decade related to the health status of older Americans. In a landmark study, researchers used the 1982 disability rates from the National Long Term Care Survey (NLTCS) for people aged 65 and older to estimate the numbers of disabled persons in each future year using census bureau projections. They then used subsequent waves of the NLTCS to determine the actual numbers of disabled persons and compared that to their estimates. Using this method, they observed 1.6 million fewer disabled older people in the U.S. in 1998 than there would have been if the disability rate had not changed since 1982.** (Chart #3) These decreases in disability have been confirmed using several independent databases and have been shown to benefit both men and women, and minority as well as non-minority populations. The latest preliminary findings from the 1999 NLTCS suggest that the rate of decline in chronic disability is continuing and may even be accelerating. Research is ongoing to understand the potentially significant long-term economic and social consequences of disability decline, including its effect on health care costs and the American workforce. Importantly, research has also begun to identify the factors contributing to the decline so that specific interventions and behavioral changes can be designed that might sustain or accelerate trends in improved function and quality of life among older Americans.

NIA encourages research with the aim of not only extending life, but also improving the quality of life. One factor contributing to a higher quality of life in later years may be a positive outlook. A recent study demonstrated that emotional vitality is associated with decreased mortality and is correlated with slower progression of disability in disabled older women (aged 65 years and older). Using data from the Women’s Health and Aging Study, a longitudinal study of disabled women, researchers found that women who were classified as emotionally vital (i.e. upbeat and positive) at the beginning of the study maintained better physical function over time than women who were not emotionally vital. Although more research is necessary to elucidate the possible role of emotions in protecting against health decline, these results suggest that helping older people maintain a high level of emotional vitality may help prevent or slow physical decline.

Many people have assumed that old age is always associated with increased disability. As little as five years ago, researchers could not conceive of an approach to preventing Alzheimer’s disease (AD). However, through research advances, the nation has renewed hope that scourges, like AD, may be treated or prevented one day. Americans can also foresee the possibility of living a long, satisfying life free of major disability. To continue its trajectory of recent success, the NIA recently released its five-year strategic plans for aging research and research into health disparities. The goals are ambitious. However, these documents provide a framework that the Institute will be using to continue the tremendous progress made in the last century. By continuing and intensifying research, NIA can move forward in meeting the promise of extended life by improving the health and well-being of older people in America.

*National Center for Health Statistics, National Vital Statistics Report, United States Life Tables, 1998, February 2001.
**National Long Term Care Survey 1982-1994 (Kenneth Manton, Ph.D.)