"Living Long Well in the 21st Century"
Living Long & Well in the 21st Century Strategic Directions for Research on Aging National Institute on Aging National Institutes of Health U.S. Department of Health and Human Services NIA Director’s Message W e are pleased to share through this document our best insights into the future of research on aging and the role of the National Institute on Aging (NIA) in realizing that future. These broad strategic goals and objectives have been identified through discussions among NIA staff members with input from the National Advisory Council on Aging, NIA’s Board of Scientific Counselors, and other representatives of the research and advocacy communities. As we look to the future, we foresee unprecedented opportunities brought about by advances in science and technology coupled with the challenge of using our best scientific judgment to make difficult choices, in some cases, about which areas of research to pursue. Our NIA intramural and extramural scientists work alongside our grantees and partners in other Institutes and Centers at the National Institutes of Health (NIH), other government agencies, and the private sector to build synergy and leverage resources to help make it possible for older adults to experience healthier, more productive lives. We strive to gain a clearer understanding of what we term “normal” aging along with deeper insights into a multitude of diseases and conditions with increased risk and severity among older adults. And we use that knowledge to develop and test more effective interventions that will indeed allow people to live long and well in the 21st century. We hope that readers will find the information in this document a useful resource for facilitating and advancing dialogue about research on aging. Richard J. Hodes, M.D. Director, National Institute on Aging November 2007 This Document Online This document is available online at www.nia.nih.gov/AboutNIA/StrategicDirections. The online version includes hyperlinks to information about NIA programs and initiatives associated with the various priority areas described in this document. Other Helpful Web Sites: National Institute on Aging Home Page – www.nia.nih.gov Current Funding Opportunities for Research and Training – www.nia.nih.gov/GrantsAndTraining NIA Extramural Research Programs – www.nia.nih.gov/ResearchInformation/ExtramuralPrograms Biology of Aging Program – www.nia.nih.gov/bap Behavioral and Social Research Program – www.nia.nih.gov/bsr Neuroscience and Neuropsychology of Aging Program – www.nia.nih.gov/nna Geriatrics and Clinical Gerontology Program – www.nia.nih.gov/gcg NIA Intramural Research Programs – www.grc.nia.nih.gov National Institutes of Health Home Page – www.nih.gov NIH Roadmap for Medical Research – nihroadmap.nih.gov NIH Blueprint for Neuroscience Research – neuroscienceblueprint.nih.gov Contents Introduction 1 Research Goals A Improve our understanding of healthy aging and disease and disability among older adults. 4 B Continue to develop and disseminate information about interventions to reduce disease and disability and improve the health and quality of life of older adults. 14 C Improve our understanding of and develop interventions to prevent and treat Alzheimer’s disease, other dementias of aging, and the aging brain. 22 D Improve our understanding of the consequences of an aging society and provide that information to inform intervention development and policy decisions. 30 E Improve our ability to reduce health disparities and eliminate health inequities among older adults. 36 Infrastructure and Resource Goal F Support the infrastructure and resources needed to promote high-quality research and communicate its results. 44 Introduction T he face of aging in the United States is changing dramatically. People are living longer, achieving higher levels of education, living in poverty less Our ability to reduce the burden of illness among older adults will depend on an increased under- standing of the dynamics of aging and how they often, and experiencing increasingly lower rates interact with various environmental and lifestyle of disability. Life expectancy nearly doubled factors in individuals. We need to explore “aging” during the 20th century with a ten-fold increase not as a single process but rather as an intricate in the number of Americans age 65 or older. Today, web of interdependent genetic, biochemical, there are approximately 35 million Americans physiological, economic, social, and psychological age 65 or older, and this number is expected to factors, some of which are better understood than double in the next 25 years. The oldest old— others. In addition to research on the biological people age 85 or older—constitute the fastest basis of aging, some scientists are working to growing segment of the U.S. population. Currently gain new insights into disease processes and about four million people, this population could comorbidities, the prevalence of which increases top 19 million by 2050. And living to 100 is with advanced age, and to use this knowledge to becoming increasingly commonplace. In 1950, develop more effective ways to prevent, diagnose, there were approximately 3,000 American centen- and treat diseases and conditions of aging. arians. By 2050, there could be nearly one million. Others are exploring behavioral and social factors The challenge for the 21st century will be to involved in aging and how they interact with make these added years as healthy and productive genetics and biology. Still others are concerned as possible and to continue the current trend with the economic and societal consequences of decline in disability across all segments of of a rapidly aging population. Building on past the population. discoveries, we will continue to focus on finding effective interventions to ensure that as people live Modern medicine and new insights into lifestyle longer, they can do so in better health and with and other environmental influences are allowing a greater independence. growing number of people to remain healthy and socially and emotionally vital into advanced ages. As life expectancy increases, however, diseases and The National Institute on Aging conditions that threaten the health of older people The National Institute on Aging leads a national remain a concern. For example, more than half scientific effort to understand the nature of aging of all Americans 65 or older show evidence of in order to promote the health and well-being of osteoarthritis in at least one joint. One in every older adults. NIA is one of the 27 Institutes and two women and one in four men over age 50 will Centers that make up the National Institutes of break a bone due to osteoporosis. Alzheimer’s Health, a component of the U.S. Department of disease (AD), cardiovascular disease, cancer, Health and Human Services. and diabetes remain widespread among older Americans. In addition, many older Americans suffer from multiple health problems, and the existence of such comorbidities often complicates treatment and can dramatically affect quality of life. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 1 NIA Research Focuses on the Increased Risk and Severity of Health Problems As People Age Older adults are healthier than ever today, cancer, and diabetes interface with occur with age—from studies of the but the risk and severity of a number of new ﬁndings about the basic processes psychological adaptation to aging diseases and conditions increase with of aging and may soon open doors for and disease to the development of age. Much of NIA-supported research personalized approaches to preempt, strategies to address the behavioral focuses on uncovering the molecular prevent, or treat these diseases across symptoms of dementia or stress. and cellular determinants of disease the lifespan. NIA-supported research also focuses risk as well as the changes that occur Better options for helping older adults on the effects of chronic illness and with age at the organ, tissue, cellular, with vision, hearing, and other the comorbidities that are so common and molecular levels that may lead to sensory disorders will dramatically among older adults. For example, NIA dysfunction. Some investigators examine improve the quality of life for these researchers are studying the demon- age-related processes from multiple individuals. strated association between certain perspectives, including those of the cardiovascular disorders such as athero- genetic, biological, clinical, behavioral, For people who suffer from bone, sclerosis (hardening of the arteries) and social, and economic sciences. Other muscle, skin, joint, and movement hyperlipidemia (elevated blood levels studies focus on speciﬁc diseases or disorders, new insights about nutrition of certain types of fat) and the risk for conditions with increased prevalence as and exercise, better surgical options, neurological disease and other age- people age. Many of the disease-speciﬁc better understanding of the basic related disorders. Others are investigat- research projects we support are collab- biology leading to new therapies, and ing the relationship between metabolic orative efforts with other Institutes at more user-friendly assistive technology disorders such as diabetes and cognitive the NIH. hold promise for helping them lead decline in older adults. more comfortable and active lives. With increasingly sophisticated tech- nological tools, we hope someday to Ongoing developments hold promise unravel the mysteries that still sur- for ﬁnding better ways to help health round Alzheimer’s disease, changes care providers and caregivers more in memory and cognition, and other effectively address a variety of age- degenerative diseases of the nervous associated disorders such as frailty, system, and to develop interventions falls, delirium, incontinence, sleep to prevent, diagnose early, and treat disturbances, and depression. these conditions. Researchers are also gaining new Exciting developments in our under- insights into the psychological, standing of cardiovascular disease, psychiatric, and social changes that 2 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging The Institute’s mission is to: mission. NIA strives to ensure that funding deci- sions and research initiatives address current and Support and conduct genetic, biological, clinical, projected public health needs and take full advan- behavioral, social, and economic research related tage of scientific and technological opportunities to the aging process, diseases and conditions for advancing the field of research on aging. With associated with aging, and other special problems constant monitoring of the health needs of our and needs of older Americans. older population and regular consultation with Foster the development of research and clinician our stakeholders, we will optimize our efforts to scientists in aging. improve the quality of life of older adults. Communicate information about aging and Our goals are to: advances in research on aging to the scientific community, health care providers, and the public. A Improve our understanding of healthy aging and disease and disability among older adults. We carry out our mission by supporting extramural research at universities and medical centers across B Continue to develop and disseminate informa- the United States and around the world and a tion about interventions to reduce disease and vibrant intramural research program at NIA disability and improve the health and quality of laboratories in Baltimore and Bethesda, Maryland. life of older adults. This document outlines the broad strategic direc- C Improve our understanding of Alzheimer’s disease, tions of the Institute and provides a point of ref- other dementias of aging, and the aging brain. erence for setting priorities and a framework for Develop drug and behavioral interventions for systematically analyzing the Institute’s scientific treating these diseases, preventing their onset and portfolio and assessing progress in achieving our progression, and maintaining cognitive, emo- tional, sensory, and motor health. D Improve our understanding of the consequences of an aging society and provide that information to inform intervention development and policy decisions. E Improve our ability to reduce health disparities and eliminate health inequities among older adults. F Support the infrastructure and resources needed to promote high-quality research and communi- cate its results. Our vision is to: Achieve a time when people in their “golden years” enjoy robust health and independence, remain physically active, and continue to make positive contributions to their families and communities. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 3 4 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Research Goal A Improve our understanding of healthy aging and disease and disability among older adults. A ging comprises a set of dynamic biological, physiological, and psychosocial processes and systems—interactive and independent—that result to and rate of progression of age-related pathologies and may contribute to frailty, independent of overt disease. This and other risk or protective processes in wide variations among individuals. Adult aging that may occur at various stages, from early life on, often involves common changes that may not be may influence health and survival outcomes in old harmful such as graying hair. For many, however, age. Many older people also suffer from anemia, aging also means a progressive and inexorable loss thrombosis, involuntary weight loss, dizziness, sen- of function leading to increased vulnerability to sory deficits such as hearing or vision loss, dementia, disease, frailty, and disability. Many hypotheses and frailty, or incontinence. Research into the underlying theories to explain this decline have been offered causes of these and other geriatric syndromes is through the years, but none by itself can explain needed in order to develop new prevention strategies the array of physical, biological, and psychological and treatment approaches. changes that take place as people age. NIA-supported research is also helping to identify NIA-supported researchers are beginning to define lifestyle factors and health behaviors that directly the link between genes and lifespan. For example, influence physical, cognitive, and emotional fitness numerous genes have been implicated in normal and risk of disease. Scientists are developing and aging processes, in age-related pathologies and dis- refining recommendations for people of all ages eases, and in the longevity of several species includ- regarding optimal diet, use of dietary supplements, ing humans. Researchers are also identifying the mental stimulation, physical exercise, quality interactions among genes; the environment; and sleep, and other healthy practices to increase their lifestyle, behavioral, and social factors and their likelihood of enjoying healthy old age. Still other influence on the initiation and progression of some researchers are looking for better ways to enhance diseases. Further research is needed to determine the physical, mental, and interpersonal abilities of the roles and interaction of these diverse factors in older people and to expand opportunities for them aging. to achieve personal goals and contribute to society in meaningful ways. As we identify more precisely One of our challenges in this research is to develop these behaviors and lifestyles that influence health a clearer understanding of the normal changes that and quality of life, we will be able to reinforce pre- accompany aging and distinguish them from the vention efforts, enhance symptom management, diseases and disabilities that are prevalent among conserve function, and improve caregiving. older adults. A common thread, for example, is the process of inflammation, which leads over time to changes in cell, tissue, and organ structure and func- tion. Inflammation may increase the susceptibility Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 5 To more fully understand aging processes and their relationship to disease and disability among older people, NIA will: Our Genes Are Key to How We Age A-1 Support studies on healthy aging, well-being, The way we age depends on a mixture of intrinsic and and longevity. extrinsic forces. Extrinsic factors such as healthy habits can be controlled. However, a signiﬁcant portion of aging is A-2 Accelerate the discovery of the causes and risk determined by genes, which may encode causative factors factors associated with disease and disability involved in aging or factors that delay aging and/or pro- among older adults. mote extended health span (longevity assurance factors). In humans, it has been estimated that genetics control 25 to 40 A-3 Encourage translational research to bridge percent of life and health span variability, but the identity of basic discovery and intervention development. the responsible genes is difﬁcult to pinpoint. Basic research- ers have identiﬁed about 100 genes that control lifespan in A-1 Support studies on healthy aging, model organisms, including roundworms called nematodes, well-being, and longevity. yeast, fruit ﬂies, and mice. Further research is needed to Research on the biology of aging has revolutionized understand the relationships among these genes and to determine whether or not the equivalent genes in humans our understanding of healthy aging. New findings function in a similar fashion. Research has also identiﬁed about genetic, molecular, and cellular factors and subtle and reversible changes in human genes, which, in processes that affect the course of aging are provid- some cases, can be passed from generation to generation ing valuable insights about aging, longevity, and and can control the level of activity of some genes. These the genesis of disease. Similarly, population studies “epigenetic” changes represent another area of research are uncovering potential risk factors such as envi- that might yield further insights into aging and age-related ronmental exposures, health-related behaviors, and disease. social factors, as well as the influence of co-existing Scientists supported by NIA are particularly interested in conditions across the lifespan and their relationship identifying genetic factors that contribute to healthy aging to the progression of disease. NIA will continue as well as unraveling the genetic and biological processes research to: involved in age-related traits and diseases. Our hope is Identify cellular and molecular factors that that the discovery and increased understanding of genes determine the pace of aging processes. involved in aging and longevity will lead to the development of medical and behavioral interventions that can slow the Researchers have identified key factors affecting aging process and, most importantly, delay or prevent the the pace of aging, including the body’s response onset of age-associated diseases. to a variety of stresses, the function of the immune system, and the role of cellular senes- cence (deterioration of the cell) as a tumor sup- decline in almost all physiological functions, pression mechanism. NIA will work to identify resulting in increased susceptibility to age-related additional factors and to elucidate the role of each chronic diseases, some functions are remarkably of these processes in the aging human. well maintained in a large number of people. Determine how the cellular and molecular bases NIA will encourage research in both the loss and of changes associated with aging contribute to maintenance of functions during the aging pro- decreased function and increased incidence of cess. Many researchers suspect that this increase disease. Although increasing age is most often in susceptibility to diseases may be due to the accompanied by a significant and progressive changes occurring as a result of the aging process itself. Therefore, manipulation of the basic 6 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging processes of aging might provide an effective way Understand the role of stem cells in tissue main- to prevent or treat age-related diseases. We will tenance and how stem cells and their environ- foster comprehensive studies both in humans and ments change with age. Stem cells contribute to in animal models to investigate the health- and tissue development and replenishment through- disease-related effects of manipulating the process out life. Stem cells are the ultimate precursors to of aging at the molecular level. all the cells of the body, and they are important tools for both cell-based therapies and regenera- Identify developmental, prenatal, early life, and tive medicine. It is clear that tissues and organs environmental processes that affect aging, age lose function with advanced age, and such losses changes, and disease. Harmful substances can may result from declines in stem cell function. exert profound physical effects on a developing This loss of function occurs at different levels, fetus, while childhood exposure to environmental including the stem cells themselves, the micro- agents such as infections or drugs can greatly limit environment where they self renew and differen- adult physical and cognitive health and longevity. tiate (the niche), the receptiveness of the target NIA will continue to support epidemiological tissues, or even in the communication among the studies to identify such factors and participate target tissues, the niches, and the stem cells. NIA in translational studies to find ways to minimize will pursue the major challenges in cell-based their effects in adults. therapies and regenerative medicine, includ- ing improvement of the mobilization of native Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 7 stem cell pools and definition of the limitations of stem cell expansion ex vivo, so that stem cells can be grown in adequate numbers for tissue repair while preserving their potency. NIA will also foster research to create a detailed molecular and functional understanding of stem cells, their niches, and their target microenvironments as well as strategies to direct stem cell differentia- tion into specific cell types. This research will inform efforts to understand and alter the aged environments that decrease stem cell function and improve the efficiency with which stem cells reach their target sites, where they can be effective while minimizing potentially harmful side effects. Understand the influence of obesity and meta- bolic status in healthy aging. We will continue collaborative studies on the relationships among obesity, insulin signaling, hypertension, and dia- betes. We will continue studies on the efficacy of various nutritional and other cognitive and behav- ioral approaches to maintaining a healthy weight and preventing cardiovascular disease, cancer, dia- and other age-associated changes. This research betes, neurodegenerative disease, musculoskeletal will provide the knowledge base necessary to conditions, and other conditions in older people. develop interventions that optimize mobility and This research will also help determine whether sensory function and prevent disease in the later or not general recommendations for healthy years of life. eating, physical exercise, and sleep in the young or middle aged are optimal for older people. Continue to support basic research in the psycho- logical science of aging. Understanding age- Understand the sensory and motor changes related psychological change remains essential for associated with aging and how they lead to advancing our understanding of how age impacts decreased function and increased incidence of behaviors and decisions that, in turn, shape the disease. Mobility changes in the aging adult can subjective well-being, social relationships, physical be age related or the precursor to more severe and mental health, physical function, and economic motor disorders. Loss of sensory functions such well-being of older adults. Advances in psycho- as vision, hearing, or the ability to taste foods logical science are needed to improve behavioral may result from aging-related processes or may be interventions, and to understand the pathways an indication of more severe underlying diseases and mechanisms through which psychological or conditions. We will promote a better under- and social factors impact health. NIA continues standing of the underlying mechanisms of these to support research on basic psychological and social processes associated with normal aging; their relationship to individual, contextual, and environmental factors that impact these outcomes; and their neurobiological and genetic basis. 8 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging • Identify factors across the lifespan that contribute to exceptional health or its decline. The study of older people is shedding light on the biological, behavioral, and social factors associated with healthy aging. We will continue research that links laboratory and longitudinal population- based studies, providing insights into the factors that define resilient individuals and contribute to well-being in old age. • Expand our knowledge of age- and longevity- associated genes as well as epigenetic alterations that affect longevity and well-being, including modes of action. NIA-supported research has shown that patterns of extreme longevity run in families. Furthermore, scientists have identified approximately 100 different genes that affect longevity in model organisms. We will continue work to identify the biological functions of longevity genes and to better understand the mechanisms of action of known and yet-to-be- identified longevity genes (longevity assurance Continue research on the impact of social genes). This research will facilitate the develop- interaction on health and well-being. ment of biologically-based interventions to pro- Although research suggests that positive social mote longevity, delay age-related dysfunction, interaction is health protective, we must extend health span, and improve the quality of improve our understanding of the mechanisms life of older people. and pathways through which these factors • Epigenetic alterations (modifications other than improve both physical and mental health. We changes in the DNA sequence that alter gene must also better identify the characteristics of expression) are also likely to play important social relationships and social environments that roles in rates of aging, age-related dysfunctions, promote healthy aging. NIA-supported research and development of age-related diseases. Like to deepen our understanding in this area will aid changes to the DNA sequence itself, epigenetic in tailoring interventions to improve the health modifications can be inherited. These modifica- and quality of life of older adults. tions affect the cellular machinery responsible for turning genes “on” or “off,” allowing or Explore the interplay between genetic, biological, preventing them from functioning optimally. clinical, social, economic, psychological, and Environmental agents such as chemicals or environmental factors affecting aging and dietary components can also modify DNA longevity. Evidence suggests that these factors and can be transmitted to offspring. and their interplay are critical to minimizing disease and achieving full potential and vitality in later years. More research is needed to verify the linkages and to better understand their underlying mechanisms. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 9 • Refine our understanding of the interplay among the biological, social, emotional, cognitive, and functional changes associated with normal aging. The impact of changes in emotional, cognitive, and physical capacities at different life stages— in combination with life course changes in motivation and goals—on social and economic behaviors at different life stages remains unknown. We know even less about changes in the neurobiological underpinnings of these interactions. NIA will use the approaches of social neuroscience and neuroeconomics to study how the neurobiological changes associated with aging influence or are influenced by social, emotional, cognitive, and motivational factors. Identify the genetic and epigenetic bases of age- • Elucidate the biological mechanisms and path- related diseases and conditions as well as factors ways through which social, psychological, and that affect disease initiation and progression. environmental stresses contribute to declines Studies of genes associated with aging processes, in health and well-being among older adults. longevity, and age-related diseases will continue to Individual differences in the subjective experience provide insights into disease pathologies and vul- and physiological and psychological impact of nerability. However, emerging research suggests stressors may exacerbate or buffer the impact that epigenetic mechanisms may also underlie, of stressors on health. We will encourage in part, the susceptibility to common and com- multi-level and interdisciplinary research in plex diseases of aging, particularly those subject collaboration with relevant NIH Institutes on to environmental influences. We will support the interactive effects of genes, behavior, and research to understand the basic mechanisms social environments on health and well-being influencing the aging process as a whole. In addi- as people age. tion, we will work to understand the interplay among genes and environmental influences, as A-2 Accelerate the discovery of the this knowledge will be essential to our under- causes and risk factors associated standing of the development of both disease and with disease and disability among healthy aging. older adults. Improve our understanding of the molecular, To develop new interventions for the prevention, genetic, cellular, and tissue bases of aging that early detection and diagnosis, and treatment of contribute to increased risk for, alter the course aging-related diseases, disorders, and disabilities, we of, and vary the response to the treatment of must first understand their causes and the factors major age-associated diseases. We will increase that place people at increased risk for their initia- efforts to understand the genetic and epigenetic tion and progression. NIA will continue research to: factors that can alter susceptibility of individuals to disease and affect the response to treatment. In addition, we will work in collaboration with other NIH Institutes and Centers to study how phenomena such as anxiety and other negative 10 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging emotions can alter nervous system function. Although these processes aid the body in respond- Inﬂammation Plays an Important ing to dangerous or stressful situations, they can damage cells, tissues, and organ systems when Role in the Aging Process produced in excess. Inﬂammation is a natural and highly regulated response that provides protection and promotes healing when infection Identify the molecular and cellular bases of age- or injury occurs. However, if left unregulated, these same related decline in immune responses. The age- processes can cause further tissue injury and damage. It related decrease in the adaptive immune response is unclear to what extent acute or chronic inﬂammation (that is, the cellular response for manufacturing inﬂuences the pace of aging. Also unknown is whether antibodies and killing pathogens) makes older age-related changes in inﬂammatory responses reﬂect a people more prone to a variety of infectious agents “normal” deterioration of cells or are the result of disease and reduces the efficacy of vaccinations in older processes, or if psychological factors such as stress could adults. These factors have a significant effect on promote the development of chronic inﬂammation or the health span and quality of life of older people. exacerbate its effects. We will support research to develop more protec- Inﬂammatory processes, particularly those resulting in tive vaccine regimens and strategies to improve chronic inﬂammation, have been implicated in a number of immune responses in the aging population. chronic diseases and conditions of aging, including cardio- vascular disease, osteoarthritis, osteoporosis, Alzheimer’s Improve our understanding of how the inflam- disease, insulin resistance and diabetes, muscle wasting, matory process is affected by aging and how and frailty. However, the precise role of inﬂammation these changes impact tissue function. The degree in each of these conditions is not well understood. NIA- to which primary age-related changes in inflam- supported researchers are working to describe more mation contribute to changes in structure and fully the underlying biology connecting the mediators of function of various tissues and organs as well as inﬂammation with these disease processes, including: the risk or progression of age-related pathologies How inﬂammatory mediators—molecules that coordinate and conditions is not clear. Likewise, researchers the inﬂammatory response at the cellular level—change are continuing to identify the sources of pro- with age, and how these changes contribute to disease inflammatory cytokines (proteins used by the body for cell-to-cell communication). We will How “normal” age-related cellular changes may trigger an examine the role of different cell types, includ- inﬂammatory response ing immune cells and adipose tissue (fat), in the How chronic or acute inﬂammation resulting from disease age-related increase in levels of pro-inflammatory or dysfunction contributes to—or protects against—further cytokines. We will also investigate how changes in cellular dysfunction the circulating levels of these cytokines contribute Ultimately, NIA-supported investigators hope to apply an to pathological changes in tissues and organs. We improved understanding of inﬂammatory processes will facilitate exploration of how the response of and their cellular mechanisms to develop more precisely different tissues to pro-inflammatory cytokines is targeted anti-inﬂammatory interventions. affected by age and how these changes contribute to the overall balance of the immune system. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 11 Identify, analyze, and track changing patterns of A-3 Encourage translational research to disability for older adults and better understand bridge basic discovery and intervention factors contributing to these patterns. The cur- development. rent pattern of increased “active life expectancy,” Translational research provides the two-way bridge the average number of years an individual will necessary to link scientific discoveries with applica- live without a limiting disease or disability in tions in medical practice and public health. For parallel with increased length of life, is threat- research on aging, basic discoveries typically begin ened by increases in obesity and disability rates with studies at a molecular or cellular level to for younger cohorts. NIA-supported research understand the mechanisms of normal aging and will address disability dynamics at several levels, disease or with studies to better understand the including longitudinal research to understand the basic behavioral and social science related to aging determinants of onset, severity, and recovery from processes. New knowledge gained at “the bench” disabling conditions. At the population level, we takes a variety of paths to human intervention stud- will foster research to understand the pathways ies—the “bedside.” Equally important is providing to disability and the causes of change in mobility a clear path back to the bench for insights gained at and function over time as well as subgroup dis- the bedside. Several NIH initiatives are focusing on parities. We will also invest in research on more the broad issues of culture change required for the sensitive measures of functional disability that are biomedical community to more successfully sup- needed to better track these changes. port translational activities. In support of our other objectives in Research Goal A, NIA will continue to: 12 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging The Quest for Biomarkers Takes Many Pathways A biomarker is a physical, biochemical, through standardized neuropsycho- ments can be used to monitor disease or functional measure used as an logical test batteries or the effect of progression. Improved brain imaging indicator of a physiological change environmental triggers or social stress promises to provide researchers with or disease process. Biomarkers— factors on aging and health outcomes. the ability to monitor how drugs affect sometimes referred to as surrogate Some biomarkers can also predict the accumulation of harmful proteins markers or clinical endpoints—can be susceptibility to disease or serve as as disease progresses. Biological used to deﬁne, diagnose, or predict measures of drug toxicity. samples from well-characterized disease and enable rational treatment patients enrolled in this and similar There is a critical lack of speciﬁc, and monitoring of disease. Basic mech- studies are made available for other reliable, quantiﬁable, and easily anistic studies of speciﬁc disorders investigations. measured biomarkers that correlate can identify molecules in biological well with early disease progression. NIA is working to improve the pre- ﬂuids, tissues, or even breath with Public and private organizations have cision and validity of biomarkers for which disease-related changes could invested heavily in identifying candi- monitoring the progression of other be identiﬁed as disease biomarkers. date disease biomarkers using tech- diseases such as osteoarthritis or Biomarker imaging tools such as nologies such as imaging, genomics, assessing an individual’s risk of cardio- positron emission tomography (PET), proteomics, and high-throughput vascular disease or diabetes. Advanced magnetic resonance imaging (MRI), approaches. NIA-supported initiatives biomarker technology also promises and nuclear magnetic resonance help to reﬁne technologies for bio- to streamline clinical trials by identi- (NMR) spectroscopy scans can reveal marker discovery and apply them to fying clinical subtypes to establish detailed alterations in tissue due to speciﬁc diseases. The Alzheimer’s more homogeneous study populations disease processes and permit non- Disease Neuroimaging Initiative, for and applying biomarker testing to invasive longitudinal tracking of example, seeks to identify whether monitor and assess the effects of disease progression. Other biomarkers longitudinal and concurrent brain trial interventions. help determine cognitive declines imaging and biochemical measure- Identify and optimize opportunities for moving and provide supplemental funding to support new knowledge from basic discovery to interven- promising interdisciplinary endeavors. tion development and back. We will accelerate Foster communication and partnerships with our efforts to promote promising preclinical other NIH Institutes and Centers and with studies and health systems research. We will other Federal agencies as well as other national also work to ensure that new technologies such and international research organizations. NIA as advanced imaging and bioinformatics and will continue to collaborate with other NIH other resources needed for effective translational Institutes and Centers on projects with a multi- research are accessible to NIA-supported scientists disciplinary focus such as the NIH Roadmap and clinicians. for Medical Research and the NIH Blueprint for Facilitate communication among NIA-supported Neuroscience Research. We will continue to parti- researchers and encourage interdisciplinary collab- cipate in partnerships with outside organizations oration. The complexity of contemporary science to share resources, support collaborative research, demands a synergistic approach to ensure collabo- eliminate barriers to drug development, and ration among researchers from multiple scientific communicate research findings to the public. disciplines along the continuum of research. We will invest in multidisciplinary research programs Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 13 14 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Research Goal B Continue to develop and disseminate information about interventions to reduce disease and disability and improve the health and quality of life of older adults. M odern medicine and new insights into lifestyle and other environmental influences promise to have a profound impact on the health and B-1 Develop effective interventions to maintain health and function and prevent or reduce the burden of well-being of older people and make it possible for age-related diseases, disorders, and them to remain physically healthy and cognitively disabilities. and emotionally vital into very advanced ages— ideally, for as long as they live. Capitalizing on Achieving and maintaining health and function new insights from basic research, NIA-supported in advanced years can be aided by physical fitness, scientists, often in collaboration with other NIH proper nutrition, and avoidance of smoking Institutes and Centers, will continue to work from and other behaviors that adversely affect health. multiple perspectives to develop and test strategies Conversely, unhealthy lifestyle choices may be for preempting or reducing the severity of the full associated with significant health problems. How- range of health problems experienced by older ever, research has shown that it is almost never people. We will work to strengthen the translation too late to decrease risk of disease and disability of basic findings in the laboratory into practical by establishing healthier patterns. Improved health applications to improve the health and quality of habits can help people survive longer, enable them life of older adults. to postpone the onset of disability, and increase quality of life and function at older ages. Research Our success will depend on progress has also shown that optimizing both the physical in achieving three objectives in this area: and social environment is important to the health B-1 Develop effective interventions to maintain and functioning of older people. health and function and prevent or reduce NIA will continue to: the burden of age-related diseases, disorders, and disabilities. Develop efficacious and cost-effective strategies for promoting and ensuring adherence to healthy B-2 Understand and develop strategies to enhance and safe behaviors among older adults. societal roles and interpersonal support for older adults, reduce social isolation, and prevent elder abuse. B-3 Increase awareness and promote adoption of interventions to improve the health and quality of life of older people. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 15 • Build on our understanding of the roles of have been established. We support studies to nutrition, obesity, sleep, and metabolic status understand the biological action of hormonal to develop more effective health maintenance changes in older men and women, assess strategies. Epidemiological studies—and, in whether or not hormone therapy will improve some cases, studies in animals—have shown health, investigate the use of compounds to clear positive effects of manipulations such produce the beneficial responses of hormones as dietary restriction and negative effects of in the body without detrimental side effects, obesity, malnutrition, and less-than-optimal and determine the potential to regulate hor- sleep patterns on health and age-related mor- mone production in specific body tissues bidity. We will use these and other findings to where increased or decreased amounts of these develop and test in clinical trials cost-effective hormones are favorable to health. dietary and other behavioral measures and • Develop strategies to reduce falls and their adherence strategies for the prevention or consequences. NIA-supported human factors delay of disease and disability. research will continue to identify safety risks for • Use our increased understanding of exercise physi- older people in home and work environments, ology and other branches of basic science to maxi- improve screening strategies, and develop mize the positive effect of exercise on older people. and disseminate information important to Several studies strongly suggest that modest reducing the risk of falls. exercise may have beneficial effects in maintain- • Explore new ways to improve safety in the home ing health—including mental health—and that and community through studies of ergonomics these benefits are possible even at advanced and the built environment. We will continue ages. For example, weight-bearing exercise can to support research to identify cost-effective build bone strength, consequently preventing alterations in design that can reduce injuries osteoporosis and subsequent fragility fractures. and provide a safer, more secure environment We will support further research to validate for older adults. exercise and exercise programs and their effects on older people within specific age groups and • Pursue a better understanding of needs and develop strategies for promoting adherence. develop interventions to improve the safety of older drivers. We will continue research to • Continue research to understand hormone changes identify factors such as visual impairment, hear- in older people and pursue the development of ing, attention, speed of processing, and other interventions to address these changes without cognitive changes that put older drivers at risk unwanted side effects. Counteracting some of automobile accidents. In addition, we will effects of aging by supplementing hormones continue to support the development of tools such as estrogen, testosterone, human growth for assessing visual, cognitive, and other abilities hormone, melatonin, and DHEA (dehydro- associated with safe driving, interventions to epiandrosterone) is an area of active study, but improve the physical and cognitive skills neces- there are concerns that individuals may be tak- sary for safe driving, and technology to support ing such agents before their safety and efficacy the special needs of older drivers. We will also support research to understand the dynamics of making the decision to stop driving, the implications of that decision for the health and well-being of older people, and alternative transportation options that help older adults maintain as much independence as possible. 16 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging This research will provide the insights needed • Test compounds that hold the promise of increasing to develop guidelines for older adults, their healthy lifespan. Promising compounds must health care providers, and family members. undergo preclinical safety and efficacy testing using animal and cellular models before being • Improve the safe use of medications by older tested in full-scale clinical trials. We will con- adults. Managing medications can be complex tinue to support the testing of promising for older people, many of whom take drugs, compounds in mice and other model systems often prescribed by more than one physician, with the long-term goal of selecting for further for multiple health problems. Complications development those most likely to have a include adverse drug interactions and interac- beneficial effect in humans. tions with dietary supplements coupled with the physiological and functional changes • Conduct clinical studies and encourage the associated with aging or age-related diseases. translation of new interventions to the clinical NIA-supported research will improve our setting. As pathways and processes of disease are understanding and maximize the effectiveness better defined, basic research findings can be of medications, develop new technical aids for translated expeditiously to the development physicians to monitor drug use, and provide of clinical applications. We will continue to new technologies and information to enable support clinical studies to improve health and patients to manage medications better and well-being through better treatments for age- avoid adverse reactions. related diseases and conditions and to test the effects of hormone therapy, dietary supplemen- Develop interventions for treating, preventing, tation, and exercise and fitness. We will work or delaying the onset of age-related diseases with others to facilitate the navigation of barri- and conditions. ers to the translation of promising compounds • Support research into the mechanisms by which into clinical trials and ultimately approval by lifestyle interventions affect aging-related changes the U.S. Food and Drug Administration. and determine how individuals can maintain function with age or regain that function after loss due to immobility, illness, or trauma. After peaking in early adulthood, most tissue func- tions decline with advancing age. This leads to increased risks for developing diseases such as cardiovascular disease and cancer, and may lead to declines in overall health and quality of life. Further research is needed on the mechanisms through which common interventions, both medical and behavioral, may slow physical and cognitive decline. NIA will continue to sup- port research into the mechanisms of functional decline and its delay, with the goals of identify- ing molecular targets for drug interventions and treatments that minimize losses and promote the recovery of function after illness or trauma. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 17 Develop improved approaches for the early services and to manage health care financing for detection and diagnosis of disabling illnesses and multiple chronic conditions. We will seek better age-related debilitating conditions. We will help interventions to help older people recognize the develop and evaluate improved techniques and implications of disease-related signs and symp- tools to measure the well-being of older people toms and consult a physician or other health care as well as symptoms of disease and disability. As provider when they first occur. And we will work new interventions are ready, we will facilitate the to find ways to help health care providers coordi- movement of biochemical, imaging, and other nate their services to older adults. technologies into mainstream medical practice, where they can be used routinely to assist in early B-2 Understand and develop strategies detection and diagnosis as well as to monitor the to enhance societal roles and inter- efficacy of interventions tested in clinical trials. personal support for older adults, reduce Find significantly improved and cost-effective social isolation, and prevent elder abuse. ways to reduce caregiver, family, and patient Despite negative stereotypes, millions of older stress and improve older people’s ability to cope people work productively and otherwise contribute with chronic disease. Families and others who to society and place a high value on retaining their care for people with chronic disease frequently independence. Research suggests that social sup- face emotional stress as well as physical and port and continued involvement in useful activities financial burdens. Investigators will continue foster positive effects both on physical and mental to evaluate strategies to improve social support, health and on longevity. This effort is especially skills training, and assistive services both for important for older adults who are at increased those who cope with chronic disease and for risk for multiple diseases, disability, and functional their caregivers. NIA-supported research will limitations that may keep them from fully engaging clarify needs and patterns of family caregiving in the world around them. Improvements in acute and how people make decisions on providing and long-term health care for older people are also care and inform guidance on support and skills, essential, including strategies to ease the burdens of including a focus on families with diverse ethnic caregivers and enhance quality of care at home and and socioeconomic backgrounds. in different long-term care settings. These initiatives should result in more effective approaches for pre- Develop strategies to improve the interaction of vention, treatment, and rehabilitation. older people with the health system. For older adults and their families, effective health care NIA will continue to: requires quality communication with and among Identify ways for older people to retain valued health care professionals. According to one study, roles and maintain independence. Older men fewer than 40 percent of people experiencing and women are now working in paid jobs, doing symptoms associated with heart and circulatory essential volunteer work, maintaining a household, or musculoskeletal systems seek a physician’s care. and/or supporting children and grandchildren. Similarly, women often avoid seeking care for NIA-supported research will seek and apply urinary incontinence. NIA will help develop technological, social, and behavioral findings to strategies to assist patients in dealing with multiple extend the ability of older adults to remain independent, active, and productive. 18 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Conduct research on the social and economic Develop strategies to help older people and their aspects of family caregiving and develop families prepare for and manage age-associated and disseminate effective interventions for changes in health, income, function, and roles. patient care in family and community settings. Older adults and family members are faced Intergenerational family support is the most with many complex decisions about retirement, common way in which a family assembles and finances, health and life insurance, and medical allocates its resources of money, skills, and time treatment. Issues of concern include the ability to care for all its members. of health care delivery systems to support patient and family needs and adherence to a patient’s • Assess and evaluate family relationships over advanced directives. NIA-supported research will time. This research will help us understand the inform decisions about complex issues of health, effects of changing relationships on the health finances, and family roles in late life, both for and well-being of older people, and gain insight individuals and policymakers. We will compile into the caregiving, emotional support, and up-to-date information about patterns of work family-level economic aspects of aging. and retirement, sources of retirement income, • Address issues centered on the increased demands intergenerational income transfers, and status of faced by family caregivers in light of changing health and disability at the regional, national, patterns of work and family demographics. We and global levels. This compilation will be used will pay particular attention to the ways in to develop and make available information and which characteristics such as gender, marital other resources for people as they plan for later status, income, socioeconomic status, race, and life transitions and possible loss of independence ethnicity influence these demands. as well as to inform policy decisions. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 19 Research and develop strategies to improve deci- sion making for long-term and end-of-life care. There is a pressing need to define organizational Dissemination of Research Results Is a mechanisms that will ensure quality, affordable health care for older people. There is also a Critical Component of the NIA Mission critical lack of empirically generated knowledge An essential component of the NIA mission is the dissemi- on how to maximize quality at the end of life. nation of information about research and aging-related topics to the general public, health professionals, the media, Medical culture is oriented primarily to patient policymakers, and advocacy organizations. The Institute care and not to addressing the multifaceted needs reaches out to the public through the NIA Web site, two of dying patients and their families. To better Information Clearinghouses with toll-free numbers, and the address these issues, we will: NIHSeniorHealth Web site. • Examine component parts of health care delivery The NIA Web site, www.nia.nih.gov, offers information systems and their impact on medical, social, func- about NIA programs, research ﬁndings, grants and train- tional, and cost outcomes and use this informa- ing opportunities, and public and professional education tion to develop interventions to improve care. materials. The NIA Spanish-language Web site, www.nia. This research will help inform the development nih.gov/Espanol has information on a wide range of of interventions to coordinate care that promotes health topics, free publications in Spanish, and links to attention to patient and family preferences, other health-related, Spanish-language Web sites. facilitates smooth transitions among care set- The NIA Information Center, 1-800-222-2225, distributes tings, and maximizes independence. We will a variety of public and professional education materials, explore ways to support long-term care, most including Age Pages on more than 40 health topics— often provided in a home setting. We will focus from arthritis and diabetes to sleep and skin care. NIA’s on interventions that reduce the burdens of evidence-based Exercise Guide provides simple, easy-to- caregivers, with an emphasis on the unique follow exercises to improve endurance, strength, ﬂexibility, challenges faced by patients with dementia and and balance. their caregivers. The Alzheimer’s Disease Education and Referral (ADEAR) • Understand caregiving patterns and improve the Center, 1-800-438-4380, offers information on diagnosis, treatment, patient care, caregiver needs, clinical trials, and effectiveness of different strategies for helping fam- research related to Alzheimer’s disease. ilies manage the care needs of the physically frail. For example, we will use knowledge gained www.NIHSeniorHealth.gov is a collaborative effort with from this research to develop and disseminate the National Library of Medicine. Based on research on evidence-based guidance on caregiving skills, cognition and aging, the site provides information on more environmental modifications, and technological than 30 health topics. Information is available in a variety supports for both informal and formal long- of senior-friendly formats, including large print, open- caption videos, and audio versions. term care settings. • Develop strategies to improve the experience of older people at the end of life. We will support of-life therapies and the cost effectiveness of research to better understand the decision- interventions to improve end-of-life care; making process and changing preferences develop better measures of end-of-life quality associated with advance care planning; better for the patient and the family to improve our understand the transitions among end-of-life understanding of psychosocial issues that impact care settings such as the home, hospital, nursing the end-of-life experience; and understand the home, and hospice; assess the benefit of end- social and economic context of caring for an older person who is dying. 20 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging • Assess the impact of health care organizations and utilizing community organizations already in place provider interactions on the quality of life for may be needed to inform, persuade, convince, and dying individuals. Special attention will be given sustain behavior change. To address these concerns to developing strategies that enhance support of and ensure that research results are disseminated to the older person, the family, and medical care all who need them, NIA will: providers who are attempting to provide humane Develop, test, and conduct health communication and life-affirming services at the end of life. programs and outreach activities to inform the Understand and develop strategies to address public about the interventions and health-related elder neglect and abuse. Although isolated studies progress validated by the results of research on have documented the devastating long-term aging. We will craft and deliver messages and consequences of elder mistreatment, research materials based on research to understand how on elder neglect and abuse has been inadequate. the target audience perceives and reacts to health We will support methodological research to help messages, how the public is persuaded to change determine the prevalence of elder physical, psycho- behavior, and how people in general, and older logical, and financial neglect and abuse. We will people in particular, respond to various media. also work to develop and disseminate reliable Develop appropriate materials and programs for measurement tools for assessing neglect and abuse a variety of target audiences. We will continue to and interventions to reduce its incidence. work to overcome gender, cultural, and language barriers to the effective communication of B-3 Increase awareness and promote health information. adoption of interventions to improve the health and quality of life of older people. Explore successful networks for the transfer of research knowledge and evaluate the usefulness Communication efforts play a critical role in of transferred interventions for older adults in educating the public about research advances to broadly designed and applied outcomes research. improve health and well-being in later life. Health NIA will continue to work with other Federal communication activities can increase the public’s agencies, State and local governments, and the awareness of a specific aging issue, problem, or private and nonprofit sectors to ensure that results solution; reinforce certain knowledge, attitudes, of research on behavioral and community inter- or health behaviors; dispel misconceptions about ventions are widely shared and have an impact on aging; and encourage individual or collective action. policies and programs. Health education programs, activities, and materials also can inform, influence, and motivate the public. Provide information to support the training of people who work with older adults. We Communicating effectively about health is chal- will provide professional societies, community lenging. Health information is often complex and organizations, and academic institutions with technical. Moreover, the information may be incon- research-based information that can be used in clusive, controversial, contradictory, or subject to training geriatricians, social workers, counselors, change as new research findings are released. Health and other community professionals and volunteers information also may conflict with long held per- to work effectively with older adults and to sonal beliefs. To succeed, health communication implement evidence-based interventions. programs and materials must be based on an appre- ciation of the needs and interests of the target audi- ence. Large scale, multi-year, multi-media efforts Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 21 22 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Research Goal C Improve our understanding of Alzheimer’s disease, other dementias of aging, and the aging brain. Develop drug and behavioral interventions for treating these diseases, preventing their onset and progression, and maintaining cognitive, emotional, sensory, and motor health. A better understanding of how the brain ages will provide important information on which to base strategies for maintaining and enhancing Our objectives in this area are to: C-1 Understand the mechanisms involved in normal brain aging; the role of cognition in cognitive, emotional, sensory, and motor function everyday functioning; protective factors for through biological and behavioral interventions. sensory, motor, emotional, and cognitive func- For example, studies have shown that new neurons tion; and the pathogenesis of AD and other form in certain regions of the brain even in adult- neurodegenerative disorders of aging. hood. This phenomenon, known as neurogenesis, suggests that medical and behavioral approaches C-2 Develop better ways of distinguishing people could be found to stimulate the formation of new with normal brain aging from those who will neurons to compensate for the loss and functional develop mild cognitive impairment (MCI), decline of neurons with aging, disease, or traumatic AD, and related conditions. injury. NIA will support research to harness func- C-3 Translate discoveries about the cellular and tional imaging and other advanced technologies molecular mechanisms of cognitive, emo- that view activity in specific regions of the brain to tional, sensory, and motor function with age identify age-related neural changes and mechanisms and the mechanisms of AD pathogenesis the older brain uses to maintain optimal learn- into diagnostic, treatment, and/or prevention ing, memory, and other cognitive functions. We strategies. will also work to clarify the interactions between the brain and the peripheral nervous, endocrine, C-4 Conduct research to better understand and hematopoietic, cardiovascular, and immune sys- develop interventions to address the special tems. We will also support the development of caregiving needs of patients with AD and preventive and therapeutic approaches to maintain- other dementias. ing health in cognition, emotion, sleep function, sensory processes, and motor function. Research on the function of the normal brain and peripheral nervous system will help us understand the ways in which non-dementia-related health outcomes arise. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 23 C-1 Understand the mechanisms involved in normal brain aging; the role of cognition in everyday functioning; protective factors for sensory, motor, emotional, and cognitive function; and the pathogenesis of AD and other neurodegenerative disorders of aging. NIA will continue research to: Improve our understanding of nervous system and behavioral changes that occur with normal aging and how brain function is maintained and enhanced. Changes in brain structure and function, some of which may compensate for age-related decrements, may continue through- out life. For example, research shows that the hippocampus, a region of the brain important for acquiring and processing information, is capable of generating new nerve cells. Furthermore, research in mice demonstrates that increased physical and mental activity started in middle age can increase hippocampal neurogenesis and decrease signs of neuronal aging. This suggests that neurogenesis may be one factor underlying the beneficial effects of an active lifestyle on brain integrity and behavioral function in humans. We will continue to explore the role of physical and mental exercise in promoting healthy cognitive, Determine how genetic, molecular, cellular, and emotional, and motor functioning and in acti- environmental factors interact for optimal brain vating the cellular machineries that protect the health and functioning, including in the oldest brain from damage and promote its repair. This old. The overall integrity of brain structure and research will help form the basis for future inves- many neural systems are largely preserved in tigation of more subtle neural changes that occur normal aging, while in age-related diseases, with age, including selective neuronal loss or specific brain cell types and their connections dysfunction that impacts memory and other are damaged or lost. Evidence suggests that functions, impaired neuronal connections, early achieving the full potential of the central and brain atrophy, and changes in the responses of peripheral nervous systems depends on develop- glial cells involved in neuron survival and brain ing the brain optimally in early life, continuing plasticity and possibly inflammation. activity to maintain function in midlife, and stimulating the brain to compensate for cell death 24 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging For example, we will: • Continue to pursue a greater understanding of the We Need To Better Distinguish interaction among genetic factors that underlie Patterns of Brain Aging normal cognitive, emotional, sensory, and motor As with other bodily organ systems, brain function declines function as well as abnormal decline and the with age. Many older people notice changes in memory, interactions between genetics and the environment. learning, or other cognitive performance. These changes are • Investigate epigenetic changes, which can signifi- associated with loss of neurons, the basic operative cells of cantly influence the structure and function of the brain. The extent of “normal” brain aging varies among individuals and can be somewhat difﬁcult to quantify. With genes within the cell. “abnormal” brain aging, however, cognitive losses are typi- • Support research to better understand the neuro- cally more severe, and after the individual dies, signiﬁcant logical and behavioral effects of environmental pathological changes related to underlying disease processes factors, both early and later in life. are usually found in the brain at autopsy. The early identi- ﬁcation of people at risk for abnormal brain aging is the In addition, we will continue to investigate the subject of intense ongoing research on genetic, biochemical, changes in brain function that take place in the and neuropsychological aspects of the transition from oldest old, people 85 or older. In the absence of normal to pathologic aging. disease, many of these individuals continue to lead Standardized neuropsychological tests have been developed healthy and productive lives even into unusually and validated with consensus thresholds of abnormal per- old age. Others, however, suffer from health condi- formance that aid clinicians in evaluating mild cognitive tions that can contribute to cognitive decline and impairment and dementia. The development of drug thera- dementia, emotional dysfunction, motor instability, pies or behavioral modiﬁcations to slow or possibly halt the and/or sensory deficits. We will work to identify complex processes involved in cognitive decline requires the and address the conditions that most affect brain earliest possible intervention. Hence researchers are search- health in this group in order to find ways to main- ing for biochemical or imaging markers that might be used tain function as long as possible. to predict the clinical course of dementia versus normal aging patterns or to monitor treatment progress. A better Understand the role of cognition in everyday understanding of factors involved in normal and abnormal functioning, including work environments, brain aging will aid our ability to enhance healthy brain decision making, and interaction with technol- aging, for example with dietary and behavioral practices ogy. NIA will support research to examine the that could prolong normal brain function. influence of contexts—behavioral, social, cultural, and technological—on the cognitive functioning of older adults; investigate the effects of age- and injury in older age. We will work to gain a related changes in cognition on activities of daily greater understanding of the many factors that living, social relationships, and health status; interact to maintain brain function, including and develop strategies for improving everyday compensatory mechanisms and adaptive or functioning through various interventions such dynamic changes. This research will enhance as cognitive training. our understanding of, and potentially our ability to prevent, brain function decline in aging and disease. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 25 Explore possible additional risk and protective factors for brain health and function, cognitive decline, mild cognitive impairment, and AD through epidemiological and other population studies. Community-based studies of aging and AD are becoming progressively more sophisti- cated. Traditional interviews, clinical evaluations, and routine laboratory tests are increasingly complemented by advanced imaging and other technologies to identify risk factors and protective factors and to relate them to specific biological mechanisms. NIA will place a special emphasis on community-based studies, including studies in racial and ethnic minority populations, capable of linking early life or midlife factors with late life cognitive decline or impairment. We will include studies of the ways that multiple factors such as lifestyle, genetics, comorbid diseases, or sensory or motor dysfunction interact to cause disease or contribute to cognitive decline. Refine our knowledge of molecular, cellular, Investigate the relationship between systemic cognitive, and other behavioral changes that metabolism and brain function during normal cause or accompany development of AD and aging and in AD. Epidemiological research has other dementias of aging. We will investigate the shown that the presence of metabolic and vascular multiple pathological changes associated with the risk factors such as obesity, diabetes, hyperten- development of AD, including accumulation of sion, and heart disease during midlife as well as abnormal proteins, loss of synapses, and death of current smoking are associated with accelerated neurons. We will promote further characterization age-related cognitive decline and with increased of these pathological changes in tissue culture, risk for AD. This association is even more pro- animal models, and humans. Our research will nounced in individuals with three or more vas- also address the behavioral and psychological cular risk factors. Given the prevalence of obesity changes associated with the development of AD and other components of metabolic syndrome in as well as psychiatric conditions such as clinical the U.S. population, we will stimulate research depression. This research will enhance our basic to examine the mechanisms by which disrupted knowledge of altered neural, cognitive, and systemic metabolism may influence the transition behavioral function in older adults and will aid between normal brain aging and AD. This effort in the development of appropriate treatments. will provide not only a better understanding of the etiology of AD, but may also benefit the search for biomarkers of cognitive aging and AD. Ultimately we are interested in exploring whether the negative impact of metabolic and vascular risk factors on brain aging can be counteracted through behavioral and lifestyle changes and the relevant mechanisms. 26 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging We will also continue to support research that for assessing cognitive function in the clinic, in examines the reciprocity of brain-body interactions the primary care setting, and in the home envi- in healthy aging and in the course of AD, especially ronment. In one project, NIA helped establish interactions mediated by stress and other hormones. the Uniform Data Set (UDS), comprising both For example, short sleep—less than an average of 6 clinical and neuropsychological tests, across all hours per night—has been associated with hormonal Alzheimer’s Disease Research Centers (ADRCs) and metabolic changes that may lead to obesity, in the United States. The UDS will promote diabetes, hypertension, increased cardiovascular uniformity in collection of cognitive function disease, or cognitive decline. data and will allow researchers to pool large sets of data across ADRCs. We will also participate C-2 Develop better ways of distinguishing in plans outlined by the recently funded NIH people with normal brain aging from Neuroscience Blueprint Toolbox project to develop those who will develop mild cognitive a measurement tool that includes a module for impairment, AD, and related conditions. assessing cognitive, sensory, motor, and emotional function in adults. A standardized assessment Successfully distinguishing people who are aging tool of this type will help researchers track and normally from those who will develop MCI—often compare behavioral change over time in longi- a precursor to AD—and AD itself is critical to pro- tudinal and epidemiological studies, in clinical moting healthy aging behaviors and the prevention, trials, and eventually in primary care and other early detection and diagnosis, and treatment of dis- non-research settings. ease. Identification of biomarkers of the transition from normal function to different levels of cognitive Improve methods of assessing changes in sensory impairment is facilitating our efforts. and motor systems as markers of age-related change and AD. Age-related changes in sensory NIA will work to: systems occur in both normal individuals and Identify neuroimaging and other biological those with AD. We will continue to examine how markers for early detection of cognitive decline, the use of sensory testing to predict early neuro- MCI, and AD and for understanding the pro- degeneration could assist in clinical diagnoses. gression from normal cognitive aging to MCI to We will also continue research to explore possible early AD. Biomarkers may be helpful in earlier correlations between changes in sensory perception and more accurate diagnosis of disease and and AD. For example, we will investigate how in tracking disease progression and treatment changes in a person’s ability to navigate visually response in clinical trials, which can decrease through the environment or changes in a person’s the time and cost of trials. sense of smell may predict the development of AD. Improve neuropsychological assessment of cognitive function. Despite remarkable advances in neuroimaging, neuropsychological assessment of cognitive function continues to be the gold standard by which AD is diagnosed. We will continue to support development of better tools Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 27 C-3 Translate discoveries about the supported trials focus on slowing the progression of cellular and molecular mechanisms of cognitive symptoms in dementia and on strategies cognitive, emotional, sensory, and motor to manage the behavioral symptoms of dementia, function with age and the mechanisms while others focus on preventing the early stages of of AD pathogenesis into diagnostic, cognitive decline. Still others combine intervention strategies such as cognitive training and standard treatment, and/or prevention strategies. drug treatments (e.g., donepezil) to improve cogni- NIA-supported studies have combined both cogni- tion in patients with dementia. tive training and standard drug treatments such as donepezil to improve memory in patients with NIA will continue to: dementia. Other NIA-supported trials focus on Stimulate translational research. We will continue slowing the progression of cognitive symptoms in to stimulate translational research aimed at dementia and on strategies to manage the behavioral discovery and preclinical development of new symptoms. Still others focus on preventing the early candidate drugs and biologics. By supporting the stages of cognitive decline. NIA-supported transla- early steps of the drug discovery and development tional studies apply the findings of basic science on process, we can play a critical role in facilitating brain mechanisms in healthy aging and in disease to the very long, difficult, and enormously expensive the identification and preclinical testing of new pre- process of translating the wealth of basic science vention and treatment strategies as a precursor to discoveries into successful AD therapeutics. We testing in human clinical trials. A number of NIA- will also support research to identify behavioral interventions aimed at maintaining brain and behavioral health and function during aging. We will apply what we are learning about the interplay among biological, behavioral, and social factors to develop more targeted and effective interventions. Support clinical trials for drug and behavioral interventions to prevent, treat, and delay the onset and progression of cognitive decline, MCI, AD, and other dementias. We will continue to support research to test promising new drug, behavioral, or combination interventions in clini- cal trials with the intention of moving them rap- idly into clinical practice. C-4 Conduct research to better under- stand and develop interventions to address the special caregiving needs of patients with AD and other dementias. A number of recent studies have demonstrated that the chronic stresses of caring for a family member with dementia can cause lasting psychological and even physical consequences. These effects are multi- fold. For example, sleep-wake patterns are altered 28 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging in AD patients, often leading to chronic sleep Develop better strategies for the care of patients deprivation in the patients and their caregivers. with MCI and AD and for alleviating caregiver Research has shown that caregivers of AD patients burden. NIA-supported investigators have devel- have an increased risk of depression, elevated stress oped a multifaceted, personalized intervention hormones, increased vulnerability to influenza, and that can significantly improve the quality of life poor wound healing (in the older caregivers). for caregivers of people with dementia. We will continue to develop and test other interventions of NIA will continue to: this type. In addition, we will research the needs Conduct research on the family and economic of long-term spousal caregivers following the burdens of AD and other dementias. Formal and death of their spouses and support development informal care for older persons with dementia is of post-bereavement interventions aimed at a major cost for families, private insurers, and the providing social support and working through public sector. We will support research at several the persistent traumatic and stressful thoughts levels, including studies on the mechanisms of the prior years of caregiving. through which the stress of caregiving affects health. We will work with others to develop new types of interventions for alleviating stress. Other studies will help us quantify and under- stand the economic burdens to inform health policy decisions. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 29 30 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Research Goal D Improve our understanding of the consequences of an aging society and provide that information to inform intervention development and policy decisions. T he greater longevity and improved health seen at older ages in many parts of the world repre- sent one of the crowning achievements of the last D-1 Understand how population aging and changes in social, economic, and demographic characteristics of cohorts century, but also present a significant challenge. reaching old age affect health and Societal aging may affect economic growth, patterns well-being in the United States and of work and retirement, the way families function, other countries. the ability of governments and communities to provide adequate resources for older people, and The social, economic, and demographic changes the prevalence of chronic disease and disability. the Nation is experiencing at the population level may have profound effects on health and well-being NIA will continue to support research on the social, at the individual level. For example, alterations in economic, and demographic consequences of the family structure may lead to changing trends in rapidly aging population in the United States and family caregiving practices, chronic diseases of aging other countries. In addition, we will continue to may become more common, and the health care support research on how social and economic factors system may experience strain as greater numbers of across the lifespan affect health and well-being Americans require services. during old age. NIA will continue to: NIA’s objectives in this area are to: Explore the effects of education and other D-1 Understand how population aging and social and demographic factors on health and changes in social, economic, and demographic well-being at older ages. Educational attainment characteristics of cohorts reaching old age is one of the strongest correlates of physical affect health and well-being in the United health and cognitive functioning at older ages. States and other countries. We will support research to unravel the reasons D-2 Understand how social, economic, and health for this connection to help project health and system factors produce disparities in health long-term care needs and devise ways to intervene at older ages and develop interventions to to reduce disparities. reduce disparities. D-3 Understand how social and economic factors throughout the lifespan affect health and well-being at older ages. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 31 Assess the impact of changing family structures on health and caregiving. Changing family structures mean that people now approaching old Understanding of age are more likely than their predecessors to be divorced, childless, or in stepfamilies. Researchers Disability Trends Provides Insights will need to examine how the presence of home- for Effective Interventions and community-based services (e.g., waiver Disability rates among older Americans—the numbers of programs, assisted living) influence the experience people unable to carry out, to speciﬁed levels, essential of family caregiving from an economic, social, activities of daily living—have declined in recent decades, and emotional perspective. Additional data are suggesting an improvement in health and function. Activities also needed to track the migration trends of of daily living assessed in these studies generally include older people as they move from community to eating, dressing, bathing, toileting, and transferring from a community as well as from independent living lying down to a sitting or standing position. Researchers sometimes also examine “instrumental activities of daily to different levels of assisted living and nursing living” like shopping or using the telephone. home care. We will support research on the ways in which the evolution of the American family The disability decline has been demonstrated in a number of structure will affect the well-being of the elderly studies, including the most recent U.S. National Long-Term by influencing living arrangements, caregiving, Care Survey. This analysis revealed that the prevalence of and economic support. chronic disability has dropped signiﬁcantly from 1982 to the present. The continuing decline in disability among older Encourage comparative analyses to evaluate the people is one of the most encouraging and important trends impact of institutions on population and indi- in the aging of the American population. However, this trend vidual well-being and foster longitudinal studies may be threatened by rising rates of obesity and sedentary on aging. Other countries have larger proportions lifestyles in children and younger adults—both risk factors for of their populations now at older ages than the late life disability. United States, and many of those with currently Continued research on the causes of disability will inform the younger populations are aging at a much more development and implementation of effective medical and rapid rate. A wide variety of institutional arrange- behavioral interventions as well as public health programs to ments for income support, home health care, promote their use. For example, the Department of Health and long-term care, and acute care have been devel- Human Services uses health and disability trend information oped in response to the challenges of population to create programs such as HealthierUS, a national effort aging. We will support comparative research on to improve people’s lives, prevent and reduce the costs of the effects of these changes on behavior, and we disease, and promote community health and wellness through will evaluate institutional reform efforts to gain physical activity, healthy diet, preventive screening, and cessa- tion of high health risk behaviors such as cigarette smoking. insights useful both in the United States and elsewhere. We will also encourage analyses on the impact of global population aging on macro- Develop a research plan to understand the economic factors and their influence on institu- dynamic changes that occur across the life tions and well-being. course. Researchers will need to understand how experiences/exposures across the life course (infancy to older age) to a variety of environmen- tal, intellectual, and social factors influence aging 32 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging and age-related well-being. We will examine D-2 Understand how social, economic, factors contributing to maintenance or decrement and health system factors produce of cognitive and physical functioning over the disparities in health at older ages and life course in an effort to forestall negative develop interventions to reduce disparities. consequences and enhance health and well-being. Health disparities continue to exist among racial, Examine the bases for individual and societal ethnic, and socioeconomic groups. Research is attitudes toward older people and develop needed to understand the causes of these disparities effective strategies to improve them. Older and how they relate to social, economic, and health people may be the target of inaccurate and system factors and develop interventions to reduce negative stereotypes. We will support research the disparities. to explore the causes of these negative attitudes and develop strategies to counter them with NIA will continue to: community and other interventions. For example, Encourage cross-national, comparative and his- engaging older people in meaningful volunteer toric research as an approach to understanding work may prove to be a “win-win” situation for the burden of disease and health disparities. society, replacing the image of dependence with Cross-national, comparative research using one of active and productive citizens. microlevel data has proven very useful in understanding how the structure of pension systems affects work and savings decisions. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 33 THE SPEED OF POPULATION AGING Many countries have already reached the stage Number of years for population age 65+ to increase of population aging that is not expected in the from 7% to 14% United States until much later in the century, and many developing countries have populations that are aging faster than in the United States. Research on long-term trends in the burden of disease and risk factors can improve projections. Comparative research on the increasing burden of chronic diseases, and on ways in which fami- lies and health care systems cope with disease management and long-term care, could provide insights useful in the United States and globally. Encourage interdisciplinary biodemographic, health systems, social, and economic perspectives to understand gender differences in health and disease at older ages. Recent demographic and economic trends have gender-specific implications for health and well-being at older ages. Non- married women, for example, are less likely than non-married men to have accumulated assets and pension wealth for use in older age, and older men are less likely to form and maintain supportive social networks. We will support research to explain how these and other factors may contribute to the differences in life expec- tancy and disability rates among men and women at older ages. This research will inform develop- ment of targeted policies to achieve dual goals of increasing longevity and delaying the onset and severity of disability. 34 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging D-3 Understand how social and work to understand the biological, behavioral, economic factors throughout the economic, and social basis for decisions of lifespan affect health and well-being individuals, employers, and families that affect at older ages. income security in retirement and the financing of long-term care. Individual differences in chances for a healthy and secure old age emerge in midlife. For example, Support research that models and measures the NIA-supported research indicates that Americans economic risks of old age with the potential in late middle age have much wider variation in for developing interventions to insure against wealth (i.e., total accumulated assets) than in these risks. Demographic and retirement income current income (i.e., earnings). Furthermore, work trends are expanding economic risks in old age. and other decisions by people in their 50s and 60s Higher life expectancy can increase the likelihood are already affected by chronic conditions and of outliving retirement savings, and the shift disability. NIA-supported research will focus on in pensions from defined benefit to defined both observational studies and interventions to contribution plans suggests that more Americans improve function based on a life course perspective. will reach retirement with Social Security as their only annuity. Although homes often represent We will continue to: the most significant part of retiree wealth, rela- Support research on social insurance and health tively few retirees make use of reverse mortgages insurance systems (e.g., Social Security and to insure against retirement income shortfalls. Medicare) to assist other agencies in promoting Many Americans will require long-term care, but the health and well-being of the elderly while few purchase private insurance to support formal ensuring program efficiency. As record numbers care expenses. Research that seeks to understand of Americans reach retirement age, programs the behavioral aspects of demand for insurance such as Social Security and Medicare will face against these old age risks and developing inter- unprecedented challenges. We will support ventions that translate findings from behavioral research to assist these and related programs to research to improve well-being will be encouraged. work as effectively and efficiently as possible to safeguard the health and well-being of older Americans. Such research will include the measurement of the economic value of good health and the development of techniques to produce National Health Accounts. Our studies on the social, educational, public health, and biomedical variables that affect length of life and rates of disability, also will inform decisions related to social and health insurance systems. We will also support continued Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 35 36 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Research Goal E Improve our ability to reduce health disparities and eliminate health inequities among older adults. D uring the 21st century, the United States will experience a dramatic increase in the propor- tion and diversity of racial and ethnic minorities We will support research to establish the scientific basis for redressing differences and inequities affecting older adult populations. We will work to in its older population. Life expectancy at older understand the extent to which genetic, behavioral, ages has increased significantly over the past 25 social, and other factors that show variation across years but unacceptable disparities continue to exist racial and ethnic groups influence health and lon- in terms of disease burden and lifespan among gevity. In addition, we will use new knowledge to racial and ethnic groups in the United States. develop behavioral and public health interventions Socioeconomic factors such as work, retirement, for reducing disparities and increasing quality of life education, income, and wealth can have a serious for all older adults. impact on health and well-being. Economic cir- Our objectives in this area are to: cumstances can determine whether an individual can afford health care and proper nutrition from E-1 Understand health differences and health early life into old age. Individual and family finan- inequities among older adults. cial resources and health insurance can determine E-2 Develop strategies to promote active life whether an older adult enters a nursing home or expectancy and improve the health status stays at home to be cared for by family and friends. of older adults in minority and other under- Health disparities are associated with a broad, com- served populations. plex, and interrelated array of factors. Diagnosis, E-3 Use research insights and advances to inform progression, response to treatment, caregiving, and policy on the health, economic status, and overall quality of life may each be affected by race, quality of life of all older adults. ethnicity, gender, socioeconomic status (SES), age, education, occupation, and other as-yet-unknown lifetime and lifestyle differences. For example, a E-1 Understand health differences and multi-ethnic epidemiological study supported by health inequities among older adults. NIA indicated that prevalence rates for Alzheimer’s There are many complex and interacting factors disease may be higher for African Americans and related to race, ethnicity, gender, environment, SES, Hispanics than for other ethnic groups. Another geography, place of birth, recency of immigration, study found striking relationships between SES and and culture that can affect the health and quality of both health and longevity. Gender differences in life of older adults. Socioeconomic factors related to health and longevity also are observed across racial work, retirement, education, income, and wealth can and ethnic groups. have a serious impact on the health and well-being We will continue to support essential research to increase our understanding of and reduce health disparities and inequities among older adults. Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 37 of the elderly. Biological and genetic factors can to utilize multiple small data sets collected by also affect the course and severity of disease many different researchers. NIA will support and disability. Furthermore, a person’s culture the use of these data to discover new scientific can have a tremendous influence on health- knowledge and to help in the evaluation and related factors such as diet and food preferences design of policies to deal with an aging society. and attitudes toward exercise. All of these factors This approach will allow data from several and their interactions must be understood in order sources to be linked by a common identifier to design effective interventions to improve health and analyzed in ways not previously possible. equity among various ethnic/racial and low SES • Use ongoing data collection programs to oversample population groups. minority populations. These data will provide To support this objective, NIA will continue important information on living arrangements, research to: income, health care needs, and other topics. Understand normal aging processes across • Continue to support surveys focused on specific various ethnic/racial and low SES populations. groups and concentrated on issues of illness and We will characterize normal processes of well-being. NIA will continue to support and aging in minority and low SES populations expand surveys of racial, ethnic, and language to increase our understanding of the course minority groups in order to provide the data of disease and disability, and to identify the needed by researchers and public policy makers. similarities and differences among racial and Determine the influences of and interactions ethnic groups and among groups living in among race, culture, ethnicity, economic different geographic locations. status, education, and work experiences in Determine the effects of early life factors on health. Health and quality of life, particularly adult health. Early life events can play an in later years, are affected by many interrelated important role in the aging process. Differences factors. NIA will learn more about risk factors in nutrition, education, disease incidence, for disease and preventive factors contributing environmental exposure and health care in fetal to good health by researching these influences development and early life can affect disease and individually and in concert. We will place a disability in later life. Research into the influence special emphasis on longitudinal data, which of early and midlife experience on the health of provide information about individuals across the aging will advance our ability to predict the their lifespans, to untangle the multitude of health status of older adults in the future. factors that affect health and well-being. Gather data that further classify patterns of health differences, inequities, and causes. E-2 Develop strategies to promote active life expectancy and improve the health • Compile data from multiple sources to assemble status of older adults in minority and the necessary volume and types of information other underserved populations. needed. Research to understand health dispari- As life expectancy increases among all population ties requires data that are accessible to researchers groups, there are more adults living with one or on a national level as well as appropriate ways more chronic conditions that may not affect the length of life but may dramatically affect qual- ity of life. Research shows that these differences 38 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging of minority older adults will facilitate the design of effective interventions to improve health status and Research Suggests a Positive quality of life for our entire aging population. Correlation between NIA will continue research to: Social Interaction and Health Track and analyze disease prevalence and course Several research studies have shown a strong correlation in diverse older adult populations. between social interaction and health and well-being • Determine the causes of disparities in the preva- among older adults and have suggested that social isolation may have signiﬁcant adverse effects for older adults. For lence of diseases and conditions such as heart example, study results indicate that: disease, obesity, hypertension, frailty, diabetes, comorbidities, and certain types of cancer among Social relationships are consistently associated with minority and underserved populations. For biomarkers of health. example, African Americans suffer from hyper- Positive indicators of social well-being may be associated tension and prostate cancer at higher rates with lower levels of interleukin-6 in otherwise healthy than their white counterparts. Hispanics suffer people. Interleukin-6 is an inﬂammatory factor implicated more from diabetes but less from heart disease. in age-related disorders such as Alzheimer’s disease, NIA-supported researchers will explore socio- osteoporosis, rheumatoid arthritis, cardiovascular disease, economic factors such as education, language, and some forms of cancer. and access to health care as well as how genetic, Some grandparents feel that caring for their grandchildren molecular, and cellular factors contribute to makes them healthier and more active. They experience differences across populations. a strong emotional bond and often lead a more active lifestyle, eat healthier meals, and may even reduce or • Determine the reasons for variation in the stop smoking. prevalence of cognitive decline and AD across population groups. We will support research Social isolation constitutes a major risk factor for to better understand the differences in the morbidity and mortality, especially in older adults. prevalence of AD among African Americans, Loneliness may have a physical as well as an emotional Asians, and Hispanics compared to non-Hispanic impact. For example, people who are lonely frequently whites. For example, Japanese Americans living have elevated systolic blood pressure. in Hawaii have lower prevalence of stroke- Loneliness is a unique risk factor for symptoms of related dementia and higher rates of AD depression, and loneliness and depression have a than Japanese nationals. We will continue to synergistic adverse effect on well-being in middle-aged examine a range of possible causes of these and older adults. disparities, including the impact of diseases such as hypertension, cardiovascular disease, More research is needed to understand the actual links to and diabetes; health behaviors; and disease positive health and determine the importance of social inter- actions as they relate to disability, falls, memory, and overall processes in minority populations. This health beneﬁts for older adults. research will draw on culturally appropriate, equivalent, and standardized measures to better understand these differences and to in active life expectancy are more marked among suggest culturally appropriate interventions. the medically underserved. Genetic, lifestyle, and socioeconomic factors also play an important role in the time of onset or severity of disease and dis- ability. NIA’s efforts to understand the special needs Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 39 Develop appropriate health strategies for disease, • Design and promote interventions appropriate illness, and disability prevention and healthy for older adults in diverse populations to more aging among the underserved. Aging Americans effectively prevent, diagnose, or reduce the effects need understandable, culturally appropriate of disease. interventions they can use to maintain and • Design and promote culturally appropriate improve their well-being. For example, adults strategies for self management of chronic diseases. with low levels of education and limited fluency in English may need specially adapted assessments • Investigate the factors affecting medication of cognitive function for the diagnosis of AD. misuse and culturally appropriate strategies for Diet and exercise recommendations may need enhancing proper use and compliance with to be adjusted to take into account religious, medication regimens. ethnic, and cultural sensitivities. Adults are more Develop interventions to improve culturally likely to use their medication appropriately if the appropriate health care delivery. labels and instructions are printed in their native language. • Design interventions to facilitate communication between health care professionals and Asian, To address these and other concerns, NIA will: Hispanic, and other elderly who have come to • Develop and promote culturally appropriate the United States with a range of educational interventions to improve healthy behaviors along and language skills. Interactions with health with strategies to increase the likelihood that these care professionals can be difficult if there are interventions will be initiated and maintained. language and cultural barriers. If the elderly individual is hospitalized or placed in a nursing home, communication becomes a critical issue in ensuring appropriate health care. NIA will 40 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging increase efforts to develop evidence-based population in research studies is essential to sound practices that will facilitate communication of research and to obtaining the results needed symptoms and care instructions between the for evidence-based intervention development. patient and the health care provider. However, historically, members of minority populations have been underrepresented in • Develop interventions to reduce health disparities clinical trials. Outreach efforts, such as involving and inequities associated with poor provider- faith-based and community organizations in patient interactions. Recent studies have revealed emphasizing the importance of medical research that how older adults are diagnosed and treated and in recruiting study participants, have had is as much a function of who they are, who is varied success in minority populations. NIA treating them, and where care is provided as will search for more effective ways to mitigate it is a function of the symptoms they present. the difficulties associated with enrollment of NIA will investigate ways to ensure that each minority individuals in research studies and individual is treated with appropriate evidence- clinical trials. For example, we will address based interventions regardless of race, ethnicity, cultural and language barriers and encourage or cultural background. effective communication of the potential benefits Develop strategies to increase inclusion of of studies and trials for improvement in health. minorities and other underserved populations Develop training programs to prepare culturally in research. proficient service providers and researchers. • Investigate novel approaches for increasing repre- We will facilitate training of researchers in the sentation and retention of minorities in research biomedical, behavioral, and social sciences as well careers. We will work to identify the best as service providers working with older adults to strategies for training and attracting a diverse help them better understand the medical implica- workforce of new, mid-career, and senior tions of the growing diversity of our population. researchers for research on aging. We will These training programs will help prepare the continue programs to assemble a cadre of next generation of our health workforce by incor- high-quality researchers through flexible porating new materials sensitive to these issues. training mechanisms that reflect the rapidly Conduct research to better understand effective changing needs of science and provide cross- strategies for communicating health messages disciplinary training. We will work to tap the that are culturally appropriate in various racial/ talents of all groups of society by encouraging ethnic and low SES populations. Because of degree-granting institutions to establish and language, educational, and cultural differences, improve programs for identifying, recruit- underserved groups do not always receive the ing, and training women and men—including information they need about healthy lifestyle minorities and individuals with disabilities— behaviors. NIA-supported communication for careers in biomedical science. We will work research with specific target audiences will assist to stimulate the training of investigators who the development of appropriate health messages can translate the findings of basic research into and dissemination channels. medical benefits for older people and expand the pool of clinical geriatric investigators. • Continue to support training for clinical staff in message development, recruitment strategies, and community and media outreach. Our ability to involve adults representative of the total Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 41 E-3 Use research insights and advances • Gather and analyze data on burdens and costs to inform policy on the health, economic of illness, healthy life expectancy, longevity, and status, and quality of life of all older adults. mortality trajectories. Determining the costs of specific illnesses has always been difficult due A key resource for understanding health disparities to the lack of adequate data on incidence and and inequities that exist among older adults is prevalence as well as inconsistencies in calcu- data on trends and patterns that can explain the lating direct and indirect medical costs. These interaction between financial assets and health difficulties are compounded in minority popu- outcomes in different racial and ethnic groups and lations by differences in use of formal medical within economically disadvantaged groups. Data care and informal family caregiving. Projections that increase our understanding of the role of of future active life expectancy, longevity, and educational status in improving health behaviors mortality depend on assumptions about how and health status will also inform the development groups of individuals will change over time, of more effective policies. particularly as recent immigrants become Minority and underserved elders depend more culturally assimilated. This research will provide heavily on Social Security, receive little support valuable information for projecting the specific from private pensions, derive less income from needs for health care services within various accumulated assets, and rely to a larger extent on population groups. earnings from employment in old age. Challenges • Develop cross-national and sub-national data- for policy makers include finding ways to encourage bases on health outcomes, risk factors, and SES individual savings and home ownership and structural factors, such as societal inequality. facilitate continued employment. Although many of the disparities in adult To support this objective, NIA will continue to: health and life expectancy across national, racial, occupational, and social class boundaries Study population changes and underlying causes are well documented, causal mechanisms are of health and function of older adults across the less well understood. NIA-supported research lifespan. Many studies have identified significant to understand these differences will be critical risk factors for the development of chronic to the development of behavioral and public diseases that pre-date onset of symptoms by at health interventions. least a decade. Population-based studies in which individuals are tracked from birth and across the Provide information useful for policy discussion lifespan help researchers understand the changes and decision making. We will continue to collect in health over time and the large variations in nationally representative longitudinal data on health across racial and ethnic populations. retirement, health insurance, savings, and family NIA-supported research will continue to develop, variables and share these data and trends with maintain, and analyze longitudinal data sets. researchers, policy analysts, and program planners. Research findings of reduced disability among Track and analyze patterns of aging and the the elderly have become prominent in the public burden of disease within and across diverse policy debate regarding Medicare and Social populations. Security. NIA will investigate whether disability is being prevented or postponed, identify contribu- tors to disability decline, determine the impact of changes in health care, and examine the economic implications of reduced rates of disability. 42 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Partnerships Strengthen NIA Research Programs The NIA research portfolio is broad Support the Study of Women’s Health Hematology, the Federation of American based and includes research related Across the Nation, a study of the Societies for Experimental Biology, the to a variety of diseases and conditions menopausal transition, along with the Foundation for the National Institutes relevant to the work of other NIH and NIH Ofﬁce of Research on Women’s of Health, the Friends of NIA, the outside organizations. This provides us Health. Gerontological Society of America, the with numerous opportunities to build National Coalition for Osteoporosis Partner with the National Library of synergy and leverage resources by part- and Related Bone Diseases, and the Medicine to develop and maintain the nering with other NIH Institutes and Population Association of America and NIHSeniorHealth Web site. Centers (ICs), other government agencies, Association of Population Centers. academic institutions, and professional NIA also partners with other govern- Pharmaceutical, biotech, and related and advocacy organizations. ment agencies on several projects private-sector companies. These including: We work closely with a number of other partnerships make tissues and NIH ICs to co-fund research initiatives, Interagency agreements with the Cen- other specimens, microarrays, rodent support meetings and conferences, ter for Medicare and Medicaid Services models, and other research resources and develop educational materials. For and the Social Security Administration available to investigators and support example, we: for collection and sharing of data major initiatives such as the Alzheim- through longitudinal studies such as er’s Disease Neuroimaging Initiative, a Co-sponsor funding opportunity the Health and Retirement Study. joint effort involving NIA, the National announcements across the full range Institute of Biomedical Imaging and of common programmatic themes. Collaborations with the National Bioengineering, non-proﬁt groups, Center for Health Statistics, the Census Collaborate with other NIH ICs on the and a number of pharmaceutical and Bureau, and others to compile and NIH Roadmap for Medical Research biotech companies. disseminate statistical information initiatives such as the NIH Director’s about aging. NIA also works closely with collaborators New Innovator Award Program and outside the United States to support an interdisciplinary program in the Partnerships to support meetings and studies to better understand the aging behavioral and social sciences. conferences such as an international experience on a global level. For summit on global aging co-sponsored Partner with other NIH ICs on NIH example, in the ongoing SardiNIA with the Department of State. Blueprint for Neuroscience Research study, Italian and NIA intramural initiatives. NIA’s private-sector partners include: investigators have a unique opportunity to identify genetic and other risk factors Co-sponsor the Osteoarthritis Initiative Nonproﬁt foundations and advocacy for aging-associated conditions in a with the National Institute of Arthritis organizations. These include the Alliance very stable population on the secluded and Musculoskeletal and Skin Diseases. for Aging Research, the Alzheimer’s island of Sardinia in the Mediterranean. Association, the Alzheimer’s Drug Partner with the National Institute NIA also co-funds more than two Discovery Foundation, the Alzheimer’s of Mental Health and the National dozen cross-national, aging-related Foundation of America, the American Institute of Neurological Disorders and datasets and single-country studies Academy of Orthopaedic Surgeons, the Stroke on the Cognitive and Emotional of aging with partners like the World American College of Sports Medicine, Health Project. Health Organization. the American Federation for Aging Research, the American Geriatrics Society, the American Society of Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 43 44 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging Goal F Support the infrastructure and resources needed to promote high-quality research and communicate its results. T he availability of the infrastructure and resources needed to support present and future research, program management, and information Continue to participate in trans-NIH efforts such as the NIH Roadmap for Medical Research and the NIH Blueprint for Neuroscience Research. dissemination is critical to the NIA mission. Partner with other government agencies, NIA must provide resources to develop a skilled professional organizations, and advocacy groups interdisciplinary research workforce, ensure that to ensure that research results are translated scientists have access to the technology and into public health programs and medical equipment they need to perform the research, practice and used to inform public policy. and facilitate the dissemination of research results to scientists, health professionals, and the public. We have five objectives to support this goal. F-3 Train and attract the diverse workforce of new, mid-career, and F-1 Foster interdisciplinary exchange senior investigators necessary for and encourage collaborative research research on aging. across disciplines. Develop and promote flexible mechanisms to meet the rapidly changing needs of science and Sponsor workshops and conferences that bring prepare scientists, clinicians, and communicators together scientists from various disciplines for to work effectively in interdisciplinary team discussion and planning. environments across the continuum of research Provide funding opportunities that encourage from basic to translational to applied. interdisciplinary efforts with co-principal Develop partnerships with academia, professional investigators and/or partnerships across two or organizations, and other entities to establish and more institutions or organizations. improve programs for identifying, recruiting, and training scholars for careers in research on aging. F-2 Engage in partnerships to create synergy and leverage resources Participate in efforts to recruit, train, and retain within and among institutions and scientists across the full spectrum of research organizations. on aging, especially targeting under-represented groups. Work closely with other NIH Institutes and Centers, and other government agencies, to Encourage the training of investigators to translate collaborate across the continuum of research from the findings of basic research into benefits for basic science through translational research to older people. clinical studies and to disseminate information about proven interventions (research translation). Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 45 F-4 Develop and distribute research resources. Support colonies of aged animal models, including genetically altered animals. These colonies are necessary for research on aging processes and specific age-related diseases. Make cell cultures and tissue, cell, and blood banks available for basic and epidemiological research. Create and make available DNA resources for genetic studies on aging and disease. Support access to imaging and other advanced technologies in shared facilities for examining aging biological systems. Support the development of population-based data sets, especially from longitudinal studies, suitable for analysis of biological, behavioral, and social factors affecting health, well-being, and functional status through the lifecourse. Support data archiving and data sharing, with adequate protections for confidentiality and privacy of research participants and their families. Support the development of internationally harmonized social and behavioral longitudinal data on aging to foster cross-national research. Support computer technologies to record Support a robust clinical trials infrastructure and analyze interdisciplinary research findings to facilitate the translation of basic research to on basic biological studies and long-term, human application in age-related diseases, and population-based data. vice versa. This support will include technical assistance for patient recruitment and retention Support candidate drug evaluation programs, of older adults in clinical trials. facilities, and related resources for animal and clinical studies. Make results of research on patient recruitment strategies widely available to the research com- Develop innovative changes in the design, plan- munity. ning, and implementation of clinical trials and social and behavioral studies on the health and Support studies on the ethical aspects of research well-being of older people. in older populations. 46 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging F-5 Disseminate information to the public, medical and scientific communities, and policy makers. Rapidly and effectively disseminate the latest advances in geriatric medicine, research on aging, and related health data through publications, professional education materials, public service announcements, and videos. Make available health information and reports of new research findings on the NIA Web site and through the NIA Information Center. Maintain and promote the NIA Alzheimer’s Disease Education and Referral (ADEAR) Center and the NIHSeniorHealth Web sites. Develop materials for special audiences and diverse populations including non-English language materials and materials for people with limited literacy. Support national education campaigns to encourage healthy practices among older adults. Support innovative programs to promote positive attitudes toward older people’s health needs on the part of health care and other service providers and the public at large. NIA and NIH Web Sites Are Valuable Sources of Health Information NIA Home Page – www.nia.nih.gov NIH Home Page – www.nih.gov NIA Publications – www.nia.nih.gov/HealthInformation Alzheimer’s Disease Education and Referral (ADEAR) Center – www.nia.nih.gov/Alzheimers NIHSeniorHealth – www.nihseniorhealth.gov NIA Spanish Home Page – www.nia.nih.gov/Espanol Living Long & Well in the 21st Century: Strategic Directions for Research on Aging 47 Acknowledgements The content of this document was developed under the guidance of staff in the NIA Office of Planning, Analysis, and Evaluation who worked closely with the leadership of the Institute to identify and carefully articulate the present and future priorities and strategic directions of NIA. NIA staff in turn looked to members of the National Advisory Council on Aging, the NIA Board of Scientific Counselors, research and advocacy organizations, and the general public for input on the draft document. In response to a request for input to our draft strategic directions issued in June of 2007, we received suggestions from 47 individuals and groups. Each provided an important perspective, and several led us to further revise the document to make it more comprehensive. We recognize below those who contributed in various ways to the content, writing, design, and production of this document. NIA Staff Contributors Alzheimer’s Disease and Other Dementias Photography Richard Hodes, Judy Salerno, and Kathie Registry, New York State Department of Health. Cover, top, photographs 1 and 3; page 4, bottom; inside American Academy of Orthopaedic Surgeons. front cover; inside back cover; page 22; page 24, top – Reed provided leadership for development courtesy of Stacy Jannis of the document. American Heart Association. American Psychological Association. American Society Cover, top, photograph 2; page 14, bottom – courtesy Felipe Sierra, Richard Suzman, Marcelle of J. Bone Miner. Res., 1986; 1:16-21 with Morrison-Bogorad, Evan Hadley, Michele for Bone and Mineral Research. Association permission from the American Society for Evans, Neil Buckholtz, Vicky Cahan, John of Directors of Geriatric Academic Programs. Bone and Mineral Research, from the National Haaga, Taylor Harden, Ron Kohanski, Colorado State University. Directors of the Institute on Aging: Aging Under the Microscope, Dan Longo, Andy Monjan, Winnie Rossi, NIA P30 Demography of Aging Centers. A Biological Quest and Molly Wagster provided scientific and Harvard Medical School. Institute for Health Cover, top, photograph 4; page i, left; page 4, top; inside Research - Kaiser Permanente. Institute for back cover, bottom; page 30, top – DigitalVision technical review in consultation with their program staff members. the Advancement of Social Work Research. Cover, top, photograph 5; page i, right; page 7, right; Johns Hopkins University. National Asso- pages 8-9, page 14, top; page 33; page 36, top – Kathie Reed, Jeannie Borger, Kate Nagy, ciation of Social Workers. National Sleep courtesy of Marty Katz Sam Speciale, Zita Givens, Loan Ta, Tamara Foundation. Oregon Health and Science Cover, middle; page 19 – ThinkStock Jones, and Ellen Silva did most of the writ- University. Orthopaedic Research Society. Cover, lower right; page 44 – Dynamic Graphics, ing and synthesis of the information along Population Association of America and the with scans on screen courtesy of William Jagust, with editorial assistance from Kathy Sorrow M.D., University of California, Berkeley, from Association of Population Centers. Portland of KLS Writing. the National Institute on Aging: Progress Report Veterans Affairs Medical Center. Saginaw on Alzheimer’s Disease 2005-2006 Karen Pocinki and Jeannie Borger coordi- Valley State University. School of Medicine - Cover, background; page ii; page iii; back cover – nated the design and final production of the Virginia Commonwealth University. Sleep courtesy of Dr. David Teplow, Harvard Medical printed document. Research Society. Society of Clinical Gero- School, from the National Institute on Aging: psychology. Stanford University. The Ameri- Progress Report on Alzheimer’s Disease 2003 National Advisory Council can Geriatrics Society. The American Society Inside front cover, left; page iv, top; page iv, bottom; on Aging – 2007 inside back cover, center right – Blue Moon of Hematology. University of California. Kenneth Brummel-Smith, John Cacioppo, University of California - Davis. University Inside front cover, top; inside back cover, top left – Peggye Dilworth-Anderson, Carl Eisdorfer, of California - San Francisco. University of Photo Researchers Inc. Larry Friedman, Mary Ganguli, Alan Garber, Illinois at Chicago. University of Maryland, Inside front cover, center right; pages 2-3; page 22, top; Paul Greengard, Michal Jazwinski, Sundeep Baltimore County. University of Massachusetts. page 26; page 47; inside back cover, center left – Khosla, Virginia Lee, Terry Mills, John University of North Carolina at Charlotte. PhotoDisc Morris, Orien Reid, Gary Ruvkun, Gerald University of Pennsylvania School of Medicine. Inside front cover, bottom; page 40 – Getty Images Schatten, Albert Siu, Mary Tinetti. University of Pittsburgh. University of Roch- Page 7, left; page 24, bottom – courtesy of Christy ester Medical Center. University of Southern Krames NIA Board of Scientific Page 10 – Photos.com Counselors – 2007 California. University of Washington. Veterans Administration Palo Alto Health Care System. Page 12; page 46 – courtesy of David M. Burton Lisa Berkman, Karen Ashe, Avery August, Page 28; back cover, left – courtesy of National West Virginia University. Western Suffolk/ Barbara Bierer, Rafael Lantigua, Gordon Institutes of Health Eastern Nassau Counties, Long Island, New Lithgow, Ron Petersen, Arlan Richardson, Page 29 – courtesy of Rick Brady York, Assisted Living Communities. Yale David Siscovick, Rudolph Tanzi, Keith University. Page 30, bottom; page 34 – courtesy of Levine and Whitfield, Ellen Wijsman. Associates, from the National Institute on Aging: Credits Why Population Aging Matters, A Global Perspective Members of Our Research and Advocacy Communities Design Page 36, bottom – courtesy of Levine and Associates, Kim Pollock, Jeffrey Dever, Dever Designs from the National Institute on Aging: Aging Individuals with the following organizations Hearts and Arteries, A Scientific Quest responded to our invitation to provide input to Project Coordinator Page 44, bottom – courtesy of Dr. Minoru Ko, the NIA Strategic Directions during May and David M. Burton, JBS International, Inc. Laboratory of Genetics, National Institute on June of 2007: Alliance for Aging Research. Aging, from: Aging Under the Microscope, A Biological Quest 48 Living Long & Well in the 21st Century: Strategic Directions for Research on Aging U.S. Department of Health and Human Services National Institutes of Health National Institute on Aging NIH Publication Number: 07-6252 November 2007