Director's Statement

Director's Statement
Alzheimer's Disease and Brain Biology Research
Biology of Aging
Reducing Disease and Disability

Charts (PDF)

• Numbers of Disabled Older Men and Women Lower than Predicted - Chart 1
• Alzheimer's Disease Prevention Initiative - Chart 2
• Growth of New Nerve Cells in the Brain - Chart 3
• Premature Aging - Werner's Syndrome and Yeast - Chart 4
• Lifestyle Changes Can Lower Need for Hypertension Medication in Order Persons - Chart 5

Director's Statement

Mr. Chairman and Members of the Committee:

The President in his FY 2000 budget has proposed that the National Institute on Aging (NIA) receive $612.6 million, an increase of $14.3 million (2.4%) over the comparable FY 1999 appropriation. Including the estimated allocation for AIDS, total support proposed for the NIA is $614.7 million, an increase of $14.4 million over the FY 1999 appropriation. Funds for NIA efforts in AIDS research are included within the Office of AIDS Research budget request.

The activities of the NIA are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for the NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan which was transmitted to Congress on September 30, 1997. The NIH's performance targets in the Plan are partially a function of resource levels requested in the President's Budget and could change based upon final Congressional Appropriations action. The NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.

I am pleased to report the NIA's recent progress, through research, toward extending the healthy, active years of life. Aging well is critical as the population of older Americans begins a rapid expansion. Fortunately, studies are showing that America's older population is becoming healthier and more fit. Previously reported findings of substantial declines in the rates of disability among older persons have recently been confirmed by an independent team of investigators using different sources of data. Notably, improvements in functioning were found to be greatest among those 80 and older, and the improvements in disability rates have accelerated from 1982 to the present. In further analyses, these decreases in disability have been documented in men and women (Chart 1 -- PDF), as well as among minorities. The NIA continues to promote research on the causes and economic consequences of the decline in disability rates with the goal of further accelerating these improvements.

Alzheimer's disease (AD), the most common form of dementia, affecting as many as four million older persons, results from abnormal changes in the brain that begin long before memory loss and other clinical symptoms become apparent. AD eventually leaves patients oblivious to the outside world and unable to perform even the most basic tasks, with devastating consequences to individuals, families, and society. During the last 20 years, scientists have produced an extraordinary body of research findings relevant to AD. Based upon these advances, the NIH is launching an AD Prevention Initiative to expedite the search for underlying causes and to make a concerted assault on disease development and progression, in collaboration with other Federal agencies and the private sector (Chart 2 -- PDF). The Prevention Initiative will invigorate efforts to discover new treatments, risk factors, methods of early detection and diagnosis, and strategies for improving patient care and alleviating caregiver burdens. The initiative will also expedite movement of promising new treatments and prevention strategies into clinical trials. For the first time, drugs will be tested in clinical trials for their ability to delay or prevent the onset of AD. The success of this initiative would thwart the impossible demands that unchecked growth of the population afflicted with AD would place on individuals, families, and society.

The AD Prevention Initiative will benefit from an explosion of findings on the underlying causes and pathology of AD. The two pathologic hallmarks that scar the brains of people with AD are senile plaques and neurofibrillary tangles. Tangles are the wreckage of microtubules that comprise the brain cells' internal transportation system. A protein known as tau normally acts to maintain the integrity of this system, and in the past year researchers provided evidence indicating that abnormalities in tau may be responsible for the formation of neurofibrillary tangles and death of brain cells. Scientists identified several mutations in the tau gene on chromosome 17 that are associated with and appear to cause one form of familial dementia, providing the first direct evidence that mutations in tau can lead to disease. Further research will target tau's role in AD and related neurodegenerative diseases, including Parkinson's disease. The NIA is collaborating closely with the National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute of Nursing Research, and other NIH institutes to stimulate rapid progress on AD, Parkinson's disease, and other neurodegenerative diseases.

Another exciting advance with great promise has overturned long-held beliefs that cells of the adult brain cannot reproduce. Investigators have shown that rodents, non-human primates, and humans make new, mature brain cells, even in older adults, in the part of the brain used in forming long-term memory. In one experiment, thousands of these cells were found to be produced each day. Intriguingly, the studies also showed that more new brain cells survived in mice exposed to stimulus-enriched environments, and that stress can substantially reduce the production of new brain cells (Chart 3 -- PDF). This finding is a major step forward, opening the way to enhancing nerve cell development and to the possibility of replacing nerve cells lost through age, trauma, or disease.

BIOLOGY OF AGING

Research on the biology of aging has led to a revolution in aging research. New findings about what causes cells to mature, to lose the capacity to reproduce, and eventually to die promise to provide valuable insights about the genesis of disease. In early 1998, major advances were made in understanding the role of telomeres, DNA segments on the ends of chromosomes that shorten with each cell division until, at a critical length, cell division ceases. Telomeres have been regarded as the cell's "molecular clock." The enzyme telomerase adds DNA segments to the ends of chromosomes, compensating for telomere loss. Researchers demonstrated that, by inserting the gene for telomerase into normal, telomerase-negative cells, shortened telomeres grow longer, and the cells replicate far beyond the limits observed for normal cells while retaining the function of young, normal cells. This finding may provide a key to unlocking a part of the biology of aging and also has important implications for cancer research.

An additional advance on aging mechanisms was recently reported for yeast. During the normal aging process, yeast cells begin to accumulate so-called DNA circles that are distinct from the DNA on chromosomes. Recently, researchers found that some yeast, with a specific gene alteration, have shorter life spans and show premature signs of aging. They discovered that this accelerated aging is associated with a more rapid accumulation of DNA circles. Scientists now think the buildup of DNA circles may be under genetic control and may function as an "aging clock" in yeast. Researchers have also discovered that the abnormal yeast gene associated with accelerated yeast aging and accumulation of DNA circles is similar to a human gene associated with Werner's syndrome, a deadly disease characterized by decreased life span and symptoms of premature aging (Chart 4 -- PDF). Lessons learned from aging yeast are thus guiding researchers' efforts to discover therapies for diseases associated with aging.

Other experimental organisms, including the worm C. elegans and the fruit fly D. melanogaster, have helped in the search for gene mutations that affect an organism's life span. This year, researchers studying fruit flies showed that the mutant methuselah gene, named for the long-lived Biblical patriarch, increases the flies' life span by an average of 35 percent over flies that lack this mutation. The mutant flies also were significantly more able to tolerate stress and heat and were more resistant to a herbicide that can damage cells. Ongoing research will attempt to identify how the methuselah gene mutation confers these characteristics more favorable for survival. This signal advance confirms the existence of genes that directly regulate aging and should lead to better understanding of mechanisms relevant to health in humans.

The technology of molecular genetics can be valuable in other aspects of aging research. For example, humans lose up to a third of skeletal muscle mass and strength as they age. In 1998, investigators successfully used a gene therapy approach in mice to show that it may be possible to prevent age-related muscle atrophy and preserve muscle size and strength in old age. The new treatment increased muscle strength by 15 percent in young adult mice and, even more strikingly, by 27 percent in older mice. For older mice, muscle strength was restored to levels equivalent to those normally observed in young adulthood. To produce these results, the researchers engineered a virus to deliver into mouse muscle a normally-occurring gene called insulin-like growth factor I (IGF-I), which plays a critical role in muscle repair and is believed to become less effective with age. While technical and ethical issues must be overcome if the procedure is to be tested in humans, this therapeutic approach has promise for reducing age-related muscle loss, for other applications involving muscle strengthening, and for treating diseases of muscle.

NIA research explores strategies that can significantly improve the quality of life of people of all ages. Exercise is a prime example of a behavior that has been proven to improve function and quality of life as we grow older. Even in the very old, simple exercises can maintain and even restore strength and stamina, flexibility, and balance. To encourage people to start an exercise habit and stick with it, the NIA, with Senator John Glenn, the National Aeronautics and Space Administration, and other Federal agency partners, launched a national education campaign on exercise for keeping fit after 50. The campaign is linked to an easy-to-follow, home-based guide to exercising that is available free of charge. The Internet version of the guide, which can be found at http://weboflife.nasa.gov/exerciseandaging/cover.html, also provides animated versions of some of the exercises.

Lifestyle changes can also be effective in reducing the risk of major disease. While blood pressure medications can substantially reduce the risk of cardiovascular disease, the leading cause of death and major cause of disability in the elderly, they can also cause adverse drug interactions and other side effects. Medications can also be very costly. The NIA and the National Heart, Lung, and Blood Institute co-funded the Trial of Nonpharmacologic Interventions in the Elderly (TONE) to test whether modest weight loss, reduction in sodium intake, or both can reduce or eliminate the need for medication in men and women ages 60 to 80 with mild high blood pressure. People who participated in the trial had previously been successful in controlling their blood pressure with a single antihypertensive medication. During the study, medication use was gradually withdrawn under medical supervision as the lifestyle changes were implemented. At the end of the trial, about one-third of the participants on either salt reduction or weight loss programs were able to maintain normal blood pressure without medication. Overweight participants who both lost weight and reduced sodium intake realized the greatest benefits; 44 percent of this group were able to control blood pressure without medication, compared with 16 percent of those receiving usual care (Chart 5 -- PDF). The TONE thus concluded that modest reduction in sodium intake and weight loss could provide a feasible, effective, and safe nonpharmacologic therapy for hypertension in a significant number of older persons who otherwise would be prescribed medications. TONE has important implications for physicians and public health professionals because it shows that older people with high blood pressure are able to make and sustain lifestyle changes. These changes are possible even after decades of relative physical inactivity and sub-optimal eating habits.

Loss of bone mass due to osteoporosis results in millions of fractures each year in the U.S., causing substantial pain, dysfunction, and death in later life. The NIA and the National Institute of Arthritis and Musculoskeletal and Skin Diseases collaborate on research to prevent osteoporosis, including studies of hormone replacement toward this end. One of these studies measured the naturally occurring internal levels of estrogen in nearly 900 women over age 65 and found that women who had measurable blood levels of estrogen--much lower than the levels currently achieved by taking hormone supplements--had less than half the risk of experiencing a subsequent hip or vertebral fracture than women with undetectable levels of estrogen in the blood. These studies suggest that even very low-dose estrogen supplements may lower the risk of postmenopausal fractures in men and women without causing adverse effects sometimes associated with estrogen therapies. NIA investigators at a Claude D. Pepper Older Americans Independence Center are conducting preliminary clinical research to investigate the impact of low-dose estrogen supplementation on markers of bone strength and turnover.

Over the past year, aging research has maintained a rapid pace of discovery in basic science and has fueled the emergence of important opportunities for interventions to delay or to prevent diseases and disabling conditions that were once thought to be a normal part of aging. These advances hold the promise of adding life to years as our nation ages. I would be happy to answer any questions.