Research Cores

Diet, Genes, and Aging Core

As both the world and U.S. elderly populations will double in the next 50 years, it is imperative to understand the biological mechanisms underlying the aging process in order to develop targeted strategies that help maintain and promote good health. In this regard, a fundamental but under-researched aspect of aging is an attenuated capacity to respond to both internal and external insults of all types. The mechanisms for this decline in stress response are not known but the variety of insults to which older adults are vulnerable is remarkable. These insults include anything from simple bone fractures to drug interactions, chronic infections and inflammation, and “metabolic stresses” where the body no longer can maintain glycemic and lipid control. These
vulnerabilities markedly increase the chances for hospitalization, disability, and death in individuals over the age of 65 and also serve as potent underlying risk factors for many diseases associated with aging, such as cardiovascular diseases (coronary artery disease, congestive heart failure, stroke), non-insulin dependent diabetes mellitus, kidney failure, neurodegenerative diseases, and carcinogenesis.

The age-related failure to respond to stresses is surprising given that the cell has an exquisite array of overlapping defenses that dispose of toxins, environmental mutagens and pathogens, as well as reactive oxygen and nitrogen species. These defenses are highly inducible, which serve effectively to resist environmental stresses and thus maintain cell and organ function. Indeed, the ability to withstand both internal and external stresses is a key factor for determining longevity. This has been attested by recent studies where lifespan of C. elegans, Drosophila, and rodents were extended when either antioxidant enzymes (catalase and superoxide dismutase) were overexpressed, when certain mutations (daf, p66shc) were introduced that increased cell resistance to insults, and when animals were placed on caloric restriction diets that maintained
metabolic efficiency even in advanced age. Thus it is striking to note that older adults, who often exhibit conditions of chronic inflammation and increased xenobiotic exposure from prescription drug intake, do not generally exhibit an induction of cellular defense mechanisms, which, would be expected to become activated.

The mechanisms involved in lost stress response are not well understood and undoubtedly multifactorial. However, Investigators of Diet, Genes and Aging Core have evidence that 1) cellular signal transduction pathways involved in activating toxicological, oxidative and metabolic stress response enzymes become attenuated in aged animals (Hagen, Stevens, Maier, Frei and Beckman) and/or 2) transcriptional dysregulation occurs thus affecting anti-stress enzyme levels (Hagen and Giebultowicz). Moreover, there is increasing awareness that nutritive factors can ameliorate vulnerability to stresses, which may provide an inexpensive, yet effective means to maintain “health-span” in older adults. Thus, on a molecular basis, the Diet, Genes, and Aging
Core investigates the mechanisms whereby stress-responses become dysregulated with age. This focus is unique among aging research centers in the U.S. and fully takes advantage of the expertise already present at OSU. This focus complements and strengthens the research agendas of both the Linus Pauling Institute and Environmental Health Sciences Center on campus. The Diet, Genes and Aging Core is also examining whether certain micronutrients (e.g., dithiol compounds,
vitamins C and E, carnitine, omega-3 fatty acids, bioflavanoids and zinc) may act as “ageessential” compounds that help maintain appropriate cellular stress responses. The outcome for these studies will, for the first time, comprehensively assess how dietary factors may slow or prevent the age-dependent decline in stress response mechanisms. The outcome from such studies is instrumental in developing therapeutic strategies designed to improve or maintain human health, thereby increasing the “healthspan” of the elderly. These nutritional strategies also serve as a bridge to the other research cores of the Center, which can be translated to outreach programs for elder care in Oregon and the U.S. This is a novel research focus that will likely lead to new insights on aging and provide a rationale for more “translational” work taking place in the Center as a whole.

Bone Health, Exercise, and Function in Aging Core

The maintenance of mobility and physical function is critical to understanding stress and adaptation in later life. Declines in mobility and physical function lead to activity restriction, dependence, disability, social isolation, and decreased quality of life. There are many and varied causes of these aging-related declines. Decreases in bone strength, muscle strength, vision, touch, position sense, balance, and flexibility all occur with older age, as do changes in movement patterns. Added to these are the effects of chronic, progressive diseases, such as arthritis. Yet, there is growing evidence that it may be possible to slow, prevent, or even reverse many aging-related physical changes through interventions that include exercise. Thus, the Bone Health, Exercise, and Function in Aging Core will take a preventative and rehabilitative approach in investigating ways by which people can develop and maintain function throughout the lifespan.

Two primary research foci of this core are the areas of fall prevention
and bone health. Every year, one in three community-dwelling older adults suffer one or more falls, and over 10% of these falls result in serious injury or death. Even noninjurious falls can decrease the quality of life, as 10-26% of older fallers restrict their activities due to fear of falling. Among the most debilitating and costly consequences of falls, however, are hip fractures. Hip fractures are associated with a 12-20% increase in mortality rate, nearly 140,000
nursing home admissions each year, and their cost exceeds $9 billion annually. Notably, over 90% of hip fractures result from a fall. In fact, two of the primary risk factors for hip fracture
are a fall to the side and decreased bone strength due to osteoporosis. Osteoporosis, a loss of bone density with age, is present in 10 million Americans over the age of 50, with another 34 million exhibiting osteopenia (low bone mass). Because a 3-5% decrease in bone density increases
the fracture risk by 20-30%, osteoporosis contributes significantly to the more than 350,000 hip fractures and 750,000 vertebral fractures that occur annually in the U.S. Preventing falls and promoting bone health are thus important components of maintaining mobility and physical function in aging.

Investigators affiliated with this core have conducted pioneering research focused on determining why older adults fall (Pavol), identifying those at greatest risk of side falls (Gunter, Snow), using high-impact exercise to prevent bone loss in postmenopausal women (Snow), studying the micromechanical behavior of trabecular bone (Bay), and identifying how genes determine bone structure (Turner). Building upon this base, current efforts are aimed at 1) identifying whether older adults can be trained to better react to prevent a fall from unpredictable balance disturbances (Pavol), 2) identifying the determinants of side-to-side stability during walking and its relationship to side fall risk (Gunter, Pavol), 3) preventing osteoporosis in older age by using jumping exercises to increase bone density during childhood (Snow, Pavol), and 4) developing better therapies to treat osteoporosis by understanding the interaction between hormones, vitamins, growth factors, drugs, and nutrition on gene expression by bone cells (Turner). The expansion of these research efforts across disciplines is one of the mandates of the incoming Director of the Bone Research Lab (Turner).

Falls and osteoporosis are not the only important concerns in maintaining mobility and physical function in older adults, however. Arthritis is the leading cause of disability in the U.S., affecting nearly 70 million adults at a cost of $125 billion annually. Patients often suffer for years before developing symptoms severe enough to justify surgery. Current studies are therefore investigating the effectiveness of resistance exercise and orthotics in preventing pain and disability in individuals with osteoarthritis (Harter, Pavol). Muscle function is also critical to mobility and physical function. As individuals age, their muscles are prone to wasting during prolonged inactivity, such as bed rest. The muscles of older adults are also more fatigable and more prone to injury during activity. In an ongoing line of research, the cellular and molecular mechanisms responsible for fatigue, adaptation to chronic non-weight bearing, and contraction-induced injury are being pursued in an animal model (Widrick). Of particular focus is the role of the calpain family of enzymes in muscle damage and the effects of diet on these enzymes.

This comprehensive and multifaceted approach to physical functioning in late life, from the molecular level through the whole-body level, and for interventions ranging from exercise to nutrition to pharmaceuticals, is a unique strength of this research core. Additional opportunities
for collaborative multidisciplinary studies exist in areas that include the interaction of exercise and diet on bone and muscle, motivation of older adults to exercise, and improving the acceptance of interventions designed to maintain function. As an example of such collaboration, faculty in EXSS, Statistics, and Engineering are currently exploring ways to make air travel more accessible for adults with disabilities (Pavol, McCubbin, Hunter-Zaworski, Lesser, Zaworski). Across these many efforts, the fundamental goal of this research core is to generate and disseminate knowledge that can be directly applied to helping people maintain their mobility and physical function over the lifespan.

Psychosocial Factors and Optimal Aging Core

The rapidly increasing growth of aging populations worldwide and the concomitant increases in burden from disease and disability make it vitally important for older adults to remain independent and productive for as long as possible. There are large individual differences in the rate at which people age, with some individuals incapacitated by age 50 and others running marathons into their 80s. Understanding the sources of individual differences in the trajectories of mental and physical health will be critical to maintaining the health of this population. Research in this core focuses on two areas: (1) stress, coping and health; and (2) the interface among physical, psychological, and social wellbeing.

The study of stress and coping has emerged as particularly important for understanding how older adults maintain physical and mental health in the face of declines in biological and cognitive systems. Psychological stress is associated with a multitude of factors related to morbidity and mortality, such as decreased immunocompetence and increased depression. Adults in seemingly similar circumstances have different responses to stresses that occur in everyday life and as part of the aging process. Stress associated with transitions unique to middle and later adulthood, such as retirement, caregiving, widowhood, or the diagnosis of chronic illness, can impact both quality of life and well-being. Personality is emerging as a crucial risk actor/protective mechanism for understanding individual differences in how older adults create and maintain healthy behaviors and healthy relationships and there is unique strength in the configuration of faculty interested in personality, health, and aging at OSU.

The interface between psychological, physical and social well-being is the second focus of this research core. A life course perspective is necessary for understanding the development of problems in mental, physical, and social functioning in late life. Social location—such as race, gender, socioeconomic status, and other contextual factors – creates cumulative advantages or disadvantages that are amplified from early adulthood to later life. Older adults with meaningful social connections who engage in productive activities maximize their “health span” as well as their lifespan. Current demographic transitions, such as changes in family structure and increasing disparities in social class challenge the social connections of older adults. For example, divorced men are at relatively high risk for social isolation in later life, and divorce is associated with both poorer health behavior habits and increased risk of morbidity and mortality. Economic changes have resulted in a greater number of families relying on two wage earners and on wage earners with more than one job. Because women provide the majority of unpaid work, their involvement in the paid labor force leaves less time for them to meet family demands. Family members, especially women, who are engaged in multiple roles, must negotiate their time
among paid work, unpaid family work, and leisure, including engaging in activities with and providing care for aging family members. A common thread for all of the researchers in this core is that they seek understanding of adaptational responses to stress in individuals and families in order to optimize aging within the unique demographic and sociohistorical context in which it occurs.

Opportunities to investigate potential linkages between stress at the biological level (with members of the Diet, Genes, and Aging Core) and stress at the psychological level will create new synergies for research that have exciting potential to influence health, as relatively little work has been done on whether psychosocial factors influence aging processes at the cellular level. Investigation of whether stress and coping processes may influence inflammatory processes is one possibility for future study. Additionally, research on motivational and social factors underlying health behaviors (e.g., physical activity, dietary choices, smoking abstinence) is an area for potential collaborative links between core members. Working with researchers in the Technology and Aging Core to determine family acceptability and use of technologies could keep older adults living independently for longer periods of time, decreasing both the emotional and financial costs of caregiving for families. Overall, the Psychosocial Core provides a critical link between the physiological and environmental factors that influence optimal aging.

Social and Ethical Issues in Technologies for Healthy Aging Core

The investigators in this core represent a unique group of researchers in Design and Human Environment (DHE) and Engineering who will examine innovations in supportive technologies to enhance living for older adults in their own homes or in residential facilities. There are excellent opportunities to partner with businesses, as exemplified by the newly created national Center for Aging Services Technology (CAST) that has brought together university researchers, technology companies, housing facility administrators, and government representatives. Using human factors and engineering technology, “smart” houses or communities can incorporate devices and computer software that allow for long-distance monitoring, establishment of behavioral “signatures” that can detect when something is amiss, and devices that prevent wandering. Biomedical sensors can be embedded in clothing and in the environment (e.g., a wall panel). These devices have the potential to allow older adults with some cognitive and/or physical deficits to remain in their home for a longer time, postponing or preventing institutionalization and increasing autonomy and independence. They also lessen stress for caregivers, as one can “check in” on a family member from a distance or feel assured that monitoring is taking place 24/7 and someone will be alerted when necessary. Companies such as Intel are invested in developing and testing supportive technologies and have built prototypes in Oregon (e.g., Oatfield Estates in Milwaukie).

Research is needed on methods for analyzing and applying monitoring data, such as software pattern recognition techniques to be able to predict regular, recurring, periodic, and/or cyclic patterns. Long-term data available on an individual level may also offer opportunities for early detection of impending health events (e.g., heart attacks or strokes). Researchers in this core plan to apply artificial intelligence techniques to identify and predict regular patterns of data so as to be able to infer whether what an individual is doing is “normal” (for a given time of day, for occasions when a given patient’s blood pressure is low, etc.). Data will be analyzed with the goal of developing ways to identify abnormal situations to determine if an intervention is in order. This would allow inference and intervention when an unusual behavioral pattern is detected, thus putting caregivers in the loop when necessary, but not requiring a caregiver to be physically on site at every moment. Such technology offers new ways to reduce labor costs, prevent medical errors, increase productivity, and increase quality of life for older adults, many of whom prefer living in a familiar home environment rather than relocating to a less desirable and more expensive residential setting.

Advanced software technologies can apply machine intelligence to tailor information display and assist individual users. No studies have yet identified the information needs and preferences of elders and their caregivers for these types of data. Studies are needed to identify the most meaningful ways to inform elders and their caregivers of status or changes in status. Individual differences in the amount and type of personal wellness information desired is likely associated with gender, culture, and socioeconomic status. Understanding these individual differences would allow software to be designed to adapt to particular consumers. Studies are also needed to investigate and characterize the needs/preferences of older consumers as compared with those of their family caregivers and healthcare professionals. Researchers in this core plan to conduct a variety of user trials (e.g., plausibility, usability, error detection, and livability studies) to evaluate the effectiveness of various interaction techniques for each audience. Guidelines can be developed that will direct appropriately designed interfaces for consumers who have (1) specific physical or cognitive impairments, (2) various degrees of familiarity and comfort with technology, or (3) different cultural/generational preferences.

While real-time sensor networks can provide biosensor, activity sensor, and behavioral diagnostic data for assessing and tracking the well-being of elders, complex issues exist with regard to privacy, autonomy, and control over monitoring, recording, and analyzing such data. Researchers in this core plan to investigate the social and ethical ramifications of health and wellness monitoring. Sensors, devices, software, and algorithms all must interface seamlessly and securely across multiple contexts. Thus, testing the efficacy of technologies for healthy aging will require multidisciplinary research and systems-level planning. A better understanding is needed of the circumstances under which data should be made available to family members, caregivers, and healthcare professionals. Studies will investigate the events or patterns that aging consumers would specify as being important for initiation of contact with a family member or healthcare professional. Generational, familial, and cultural differences likely play into what is seen as necessary, acceptable, and desirable and these factors will be carefully assessed.

Advanced technologies can also enable elders to remain independent or quasi-independent for much longer than traditional approaches. But it is not clear that such technologies can be made sufficiently unobtrusive and appealing for aging consumers. How can technology best enhance an individual’s sense of independence/autonomy, while maintaining high standards of health and safety? How can monitoring technologies be designed and marketed to appeal to older consumers who may be unfamiliar or uncomfortable with computers and other advanced technologies? Researchers in this core will identify the factors that make advanced technologies more/less appealing to older adults and help reduce the types of “social stigma” traditionally associated with assistive devices designed for aging consumers. Collaborative opportunities are currently being pursued (described below) with Intel and HP. Potential joint projects between researchers in the Psychosocial Factors and Optimal Aging Core revolve around measurement of change in mental and physical health of older adults and family members when technology is integrated into caregiving. Including expertise of faculty in the Bone Health, Exercise and Function in Aging Core would also be helpful in the conceptualization and design of technological products aimed at improving physical functioning. The overall goal of researchers in this core is to partner with others, including industry, to develop products designed to enhance quality of life and to understand preferences of older adults and family members for these technologies.