Special Topics

• With increasingly sophisticated technological tools, we hope someday to unravel the mysteries that still surround Alzheimer’s disease, changes in memory and cognition, and other degenerative diseases of the nervous system, and to develop interventions to prevent, diagnose early, and treat these conditions.
• Exciting developments in our understanding of cardiovascular disease, cancer, and diabetes interface with new findings about the basic processes of aging and may soon open doors for personalized approaches to preempt, prevent, or treat these diseases across the lifespan.
• Better options for helping older adults with vision, hearing, and other sensory disorders will dramatically improve the quality of life for these individuals.
• For people who suffer from bone, muscle, skin, joint, and movement disorders, new insights about nutrition and exercise, better surgical options, better understanding of the basic biology leading to new therapies, and more user-friendly assistive technology hold promise for helping them lead more comfortable and active lives.
• Ongoing developments hold promise for finding better ways to help health care providers and caregivers more effectively address a variety of age-associated disorders such as frailty, falls, delirium, incontinence, sleep disturbances, and depression.
• Researchers are also gaining new insights into the psychological, psychiatric, and social changes that occur with age—from studies of the psychological adaptation to aging and disease to the development of strategies to address the behavioral symptoms of dementia or stress.

NIA-supported research also focuses on the effects of chronic illness and the comorbidities that are so common among older adults. For example, NIA researchers are studying the demonstrated association between certain cardiovascular disorders such as atherosclerosis (hardening of the arteries) and hyperlipidemia (elevated blood levels of certain types of fat) and the risk for neurological disease and other age-related disorders. Others are investigating the relationship between metabolic disorders such as diabetes and cognitive decline in older adults.

The way we age depends on a mixture of intrinsic and extrinsic forces. Extrinsic factors such as healthy habits can be controlled. However, a significant portion of aging is determined by genes, which may encode causative factors involved in aging or factors that delay aging and/or promote extended health span (longevity assurance factors). In humans, it has been estimated that genetics control 25 to 40 percent of life and health span variability, but the identity of the responsible genes is difficult to pinpoint. Basic researchers have identified about 100 genes that control lifespan in model organisms, including roundworms called nematodes, yeast, fruit flies, and mice. Further research is needed to understand the relationships among these genes and to determine whether or not the equivalent genes in humans function in a similar fashion. Research has also identified subtle and reversible changes in human genes, which, in some cases, can be passed from generation to generation and can control the level of activity of some genes. These “epigenetic” changes represent another area of research that might yield further insights into aging and age-related disease.

Scientists supported by NIA are particularly interested in identifying genetic factors that contribute to healthy aging as well as unraveling the genetic and biological processes involved in age-related traits and diseases. Our hope is that the discovery and increased understanding of genes involved in aging and longevity will lead to the development of medical and behavioral interventions that can slow the aging process and, most importantly, delay or prevent the onset of age-associated diseases.

Inflammation is a natural and highly regulated response that provides protection and promotes healing when infection or injury occurs. However, if left unregulated, these same processes can cause further tissue injury and damage. It is unclear to what extent acute or chronic inflammation influences the pace of aging. Also unknown is whether age-related changes in inflammatory responses reflect a “normal” deterioration of cells or are the result of disease processes, or if psychological factors such as stress could promote the development of chronic inflammation or exacerbate its effects.

Inflammatory processes, particularly those resulting in chronic inflammation, have been implicated in a number of chronic diseases and conditions of aging, including cardiovascular disease, osteoarthritis, osteoporosis, Alzheimer’s disease, insulin resistance and diabetes, muscle wasting, and frailty. However, the precise role of inflammation in each of these conditions is not well understood. NIA-supported researchers are working to describe more fully the underlying biology connecting the mediators of inflammation with these disease processes, including:

• How inflammatory mediators—molecules that coordinate the inflammatory response at the cellular level—change with age, and how these changes contribute to disease
  
  
• How “normal” age-related cellular changes may trigger an inflammatory response
  
  
• How chronic or acute inflammation resulting from disease or dysfunction contributes to—or protects against—further cellular dysfunction

Ultimately, NIA-supported investigators hope to apply an improved understanding of inflammatory processes and their cellular mechanisms to develop more precisely targeted anti-inflammatory interventions.

A biomarker is a physical, biochemical, or functional measure used as an indicator of a physiological change or disease process. Biomarkers—sometimes referred to as surrogate markers or clinical endpoints—can be used to define, diagnose, or predict disease and enable rational treatment and monitoring of disease. Basic mechanistic studies of specific disorders can identify molecules in biological fluids, tissues, or even breath with which disease-related changes could be identified as disease biomarkers. Biomarker imaging tools such as positron emission tomography (PET), magnetic resonance imaging (MRI), and nuclear magnetic resonance (NMR) spectroscopy scans can reveal detailed alterations in tissue due to disease processes and permit non-invasive longitudinal tracking of disease progression. Other biomarkers help determine cognitive declines through standardized neuropsychological test batteries or the effect of environmental triggers or social stress factors on aging and health outcomes. Some biomarkers can also predict susceptibility to disease or serve as measures of drug toxicity.

There is a critical lack of specific, reliable, quantifiable, and easily measured biomarkers that correlate well with early disease progression. Public and private organizations have invested heavily in identifying candidate disease biomarkers using technologies such as imaging, genomics, proteomics, and high-throughput approaches. NIA-supported initiatives help to refine technologies for biomarker discovery and apply them to specific diseases. The Alzheimer’s Disease Neuroimaging Initiative, for example, seeks to identify whether longitudinal and concurrent brain imaging and biochemical measurements can be used to monitor disease progression. Improved brain imaging promises to provide researchers with the ability to monitor how drugs affect the accumulation of harmful proteins as disease progresses. Biological samples from well-characterized patients enrolled in this and similar studies are made available for other investigations.

NIA is working to improve the precision and validity of biomarkers for monitoring the progression of other diseases such as osteoarthritis or assessing an individual’s risk of cardiovascular disease or diabetes. Advanced biomarker technology also promises to streamline clinical trials by identifying clinical subtypes to establish more homogeneous study populations and applying biomarker testing to monitor and assess the effects of trial interventions.

An essential component of the NIA mission is the dissemination of information about research and aging-related topics to the general public, health professionals, the media, policymakers, and advocacy organizations. The Institute reaches out to the public through the NIA Web site, two Information Clearinghouses with toll-free numbers, and the NIHSeniorHealth Web site.

The NIA Web site, www.nia.nih.gov, offers information about NIA programs, research findings, grants and training opportunities, and public and professional education materials. The NIA Spanish-language Web site, www.nia.nih.gov/Espanol has information on a wide range of health topics, free publications in Spanish, and links to other health-related, Spanish-language Web sites.

The NIA Information Center, 1-800-222-2225, distributes a variety of public and professional education materials, including Age Pages on more than 40 health topics—from arthritis and diabetes to sleep and skin care. NIA’s evidence-based Exercise Guide provides simple, easy-to-follow exercises to improve endurance, strength, flexibility, and balance.

The Alzheimer’s Disease Education and Referral (ADEAR) Center, 1-800-438-4380, offers information on diagnosis, treatment, patient care, caregiver needs, clinical trials, and research related to Alzheimer’s disease.

www.NIHSeniorHealth.gov is a collaborative effort with the National Library of Medicine. Based on research on cognition and aging, the site provides information on more than 30 health topics. Information is available in a variety of senior-friendly formats, including large print, open-caption videos, and audio versions.

As with other bodily organ systems, brain function declines with age. Many older people notice changes in memory, learning, or other cognitive performance. These changes are associated with loss of neurons, the basic operative cells of the brain. The extent of “normal” brain aging varies among individuals and can be somewhat difficult to quantify. With “abnormal” brain aging, however, cognitive losses are typically more severe, and after the individual dies, significant pathological changes related to underlying disease processes are usually found in the brain at autopsy. The early identification of people at risk for abnormal brain aging is the subject of intense ongoing research on genetic, biochemical, and neuropsychological aspects of the transition from normal to pathologic aging.

Standardized neuropsychological tests have been developed and validated with consensus thresholds of abnormal performance that aid clinicians in evaluating mild cognitive impairment and dementia. The development of drug therapies or behavioral modifications to slow or possibly halt the complex processes involved in cognitive decline requires the earliest possible intervention. Hence researchers are searching for biochemical or imaging markers that might be used to predict the clinical course of dementia versus normal aging patterns or to monitor treatment progress. A better understanding of factors involved in normal and abnormal brain aging will aid our ability to enhance healthy brain aging, for example with dietary and behavioral practices that could prolong normal brain function.

Disability rates among older Americans—the numbers of people unable to carry out, to specified levels, essential activities of daily living—have declined in recent decades, suggesting an improvement in health and function. Activities of daily living assessed in these studies generally include eating, dressing, bathing, toileting, and transferring from a lying down to a sitting or standing position. Researchers sometimes also examine “instrumental activities of daily living” like shopping or using the telephone.

The disability decline has been demonstrated in a number of studies, including the most recent U.S. National Long-Term Care Survey. This analysis revealed that the prevalence of chronic disability has dropped significantly from 1982 to the present. The continuing decline in disability among older people is one of the most encouraging and important trends in the aging of the American population. However, this trend may be threatened by rising rates of obesity and sedentary lifestyles in children and younger adults—both risk factors for late life disability.

Continued research on the causes of disability will inform the development and implementation of effective medical and behavioral interventions as well as public health programs to promote their use. For example, the Department of Health and Human Services uses health and disability trend information to create programs such as HealthierUS, a national effort to improve people’s lives, prevent and reduce the costs of disease, and promote community health and wellness through physical activity, healthy diet, preventive screening, and cessation of high health risk behaviors such as cigarette smoking.

Several research studies have shown a strong correlation between social interaction and health and well-being among older adults and have suggested that social isolation may have significant adverse effects for older adults. For example, study results indicate that:

• Social relationships are consistently associated with biomarkers of health.
  
  
• Positive indicators of social well-being may be associated with lower levels of interleukin-6 in otherwise healthy people. Interleukin-6 is an inflammatory factor implicated in age-related disorders such as Alzheimer’s disease, osteoporosis, rheumatoid arthritis, cardiovascular disease, and some forms of cancer.
  
  
• Some grandparents feel that caring for their grandchildren makes them healthier and more active. They experience a strong emotional bond and often lead a more active lifestyle, eat healthier meals, and may even reduce or stop smoking.
  
  
• Social isolation constitutes a major risk factor for morbidity and mortality, especially in older adults.
  
  
• Loneliness may have a physical as well as an emotional impact. For example, people who are lonely frequently have elevated systolic blood pressure.
  
  
• Loneliness is a unique risk factor for symptoms of depression, and loneliness and depression have a synergistic adverse effect on well-being in middle-aged and older adults.

More research is needed to understand the actual links to positive health and determine the importance of social interactions as they relate to disability, falls, memory, and overall health benefits for older adults.

The NIA research portfolio is broad based and includes research related to a variety of diseases and conditions relevant to the work of other NIH and outside organizations. This provides us with numerous opportunities to build synergy and leverage resources by partnering with other NIH Institutes and Centers (ICs), other government agencies, academic institutions, and professional and advocacy organizations.

We work closely with a number of other NIH ICs to co-fund research initiatives, support meetings and conferences, and develop educational materials. For example, we:

• Co-sponsor funding opportunity announcements across the full range of common programmatic themes.
  
  
• Collaborate with other NIH ICs on the NIH Roadmap for Medical Research initiatives such as the NIH Director’s New Innovator Award Program and an interdisciplinary program in the behavioral and social sciences.
  
  
• Partner with other NIH ICs on NIH Blueprint for Neuroscience Research initiatives.
  
  
• Co-sponsor the Osteoarthritis Initiative with the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
  
  
• Partner with the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke on the Cognitive and Emotional Health Project.
  
  
• Support the Study of Women’s Health Across the Nation, a study of the menopausal transition, along with the NIH Office of Research on Women’s Health.
  
  
• Partner with the National Library of Medicine to develop and maintain the NIHSeniorHealth Web site.

NIA also partners with other government agencies on several projects including:

• Interagency agreements with the Center for Medicare and Medicaid Services and the Social Security Administration for collection and sharing of data through longitudinal studies such as the Health and Retirement Study.
  
  
• Collaborations with the National Center for Health Statistics, the Census Bureau, and others to compile and disseminate statistical information about aging.
  
  
• Partnerships to support meetings and conferences such as an international summit on global aging co-sponsored with the Department of State.

NIA’s private-sector partners include:

• Nonprofit foundations and advocacy organizations. These include the Alliance for Aging Research, the Alzheimer’s Association, the Alzheimer’s Drug Discovery Foundation, the Alzheimer’s Foundation of America, the American Academy of Orthopaedic Surgeons, the American College of Sports Medicine, the American Federation for Aging Research, the American Geriatrics Society, the American Society of Hematology, the Federation of American Societies for Experimental Biology, the Foundation for the National Institutes of Health, the Friends of NIA, the Gerontological Society of America, the National Coalition for Osteoporosis and Related Bone Diseases, and the Population Association of America and Association of Population Centers.
  
  
• Pharmaceutical, biotech, and related private-sector companies. These partnerships make tissues and other specimens, microarrays, rodent models, and other research resources available to investigators and support major initiatives such as the Alzheimer’s Disease Neuroimaging Initiative, a joint effort involving NIA, the National Institute of Biomedical Imaging and Bioengineering, non-profit groups, and a number of pharmaceutical and biotech companies.