The Need as Indicated by the Stakeholders/Statement of the Problem


Midlife and older adults comprise the fastest growing population segment in the US. The baby boomers, who make-up much of this population shift [1], have higher rates of obesity, chronic disease and disabilities than previous generations [2]. Older adults are at higher risk for developing arthritis, sarcopenia, diabetes, hypertension, hypercholesterolemia, age-related macular degeneration (AMD), and cardiovascular disease (CVD) than younger adults. These conditions that are associated with disabilities, compromise physical capacity and loss of independence [3] but are preventable by diet or/and physical activity.


This proposal outlines a transdisciplinary research plan to identify integrated and holistic approaches to improve the health and wellness of midlife and aging adults. Essential to this proposal is the understanding that successful aging underscores independence. The aim of this project, building on the teams previous work, is to use an integrated approach in multiple populations (e.g., rural- and urban residing, and ethnically and socioeconomically diverse), to address the known antecedents for chronic diseases that impact older adults. The long-term goal of this work is to attenuate the impact of aging and reduce the incidence of obesity and chronic disease through research-based and sustainable interventions using a holistic approach comprised of molecular and mechanistic studies, environmental assessments, lifestyle needs assessments and theory-based lifestyle interventions that result in measurable behavior (See Logic Model).


The Importance of the Research/Justification


The National Research Council identified Understanding Individual Health as a challenge in A New Biology for the 21st Century [4]; specifically, how best to utilize scientific advances within complex systems [4], such as human aging. The proposed research also addresses two USDA-NIFA priority areas: 1) food security and hunger and 2) obesity. This multistate teams current and future research investigates how lifestyle choices, such as diet quality and physical activity, impact food security, and individual health and well-being.

Adults make daily food and activity choices without being aware of how these seemingly inconsequential decisions impact their health. Numerous biological, environmental and behavioral factors influence an individuals daily health choices. Especially as the older adult population grows in the US, so will the aforementioned age-related diseases. This also led us to look into midlife adults as they are more likely than the previous generation to have these conditions and increased obesity. If no action taken when they reach old age, it can create a public health burden that could reverse recent advances in chronic disease prevention [5]. To better understand the factors influencing age-related diseases and health-promotion in midlife and older adults, this multistate research project will examine: Area 1) molecular and mechanistic understanding of how nutrients and activity can influence age-related diseases; Area 2) environmental factors influencing the adoption of health-promoting lifestyle changes and Area 3) lifestyle needs assessment and evaluation of lifestyle interventions that lead to measurable outcomes. The proposed experiments under each of these study areas, either directly or indirectly, address obesity and sustainable chronic disease reduction in midlife and older adults (See Concept Map).


STUDY AREA 1: MOLECULAR AND MECHANISTIC UNDERSTANDING OF AGE-RELATED DISEASES


Telomere Health and Health Trajectory of Older Adults
There is a strong relationship among the circadian clock, aging, obesity, CVD, cancer and other maladies. The molecular mechanisms are multifactorial that include increased oxidative, genotoxic stress and misregulation of metabolism [6-8]. Numerous funding agencies support studies in model organisms such as Neurospora, Drosophila, zebrafish and mice to propel our understanding human disease progression. We have recently determined that the clock transcription factors are localized to the telomeres in Neurospora crassa and preliminary evidence indicates this is evolutionarily conserved in mammals. Our hypothesis is that diets with increased fruits, vegetables and whole grains will help prevent telomere shortening and the clock assists in this process. When individuals consume high fat diets, reactive oxygen species (ROS) levels are elevated and this contributes to numerous metabolic syndromes and the overall aging process. Telomeres are especially sensitive to elevated ROS and antioxidants help maintain telomere length and telomeres are an important genetic element linked to aging [9]. Our goal is to explore the combined effect of telomeres length, genotoxic compounds like ROS and the circadian clock in individuals who consume poor diets relative to those who eat diets rich in whole-grains, fruits, and vegetables.


Bmal1 (a core component of the clock) knockout mice have an advanced aging phenotype and supplementing their diet with the antioxidant N-acetyl-L-cysteine can increase longevity and reduce age-related pathologies [10]. This represents a possible connection among diet, aging, and the circadian clock where foods higher in antioxidants like fruits, vegetables and whole grains with their elevated glutathione and other natural antioxidants like flavonoids, and carotenoids have a positive impact on genome health, compared to high fat diets that when broken-down increase oxidative stress and cause adverse affects. Intercellular ROS is a genotoxic stress that increases mutagenesis and causes telomere shortening which is a molecular hallmark of aging and age related diseases. The circadian clock combats elevated ROS through its control of central metabolism, and antioxidant enzymes such as superoxide dismutase and catalyase. In addition, the clock is responsive to ROS indicting an interconnected circuit that is influenced by diet. Prolonged and elevated oxidative stress causes shortening of telomere and telomere shortening is observed in many metabolic syndromes including obesity [11]. Therefore understanding the connection among diet, age-related metabolic syndromes, telomere destruction, telomerase activation, and circadian clock is critical to improve the health trajectory of older adults. The experiments listed below are foundational in nature, not pinnacle, because this is the first study linking the circadian clock, telomere stability, healthy aging that factor dietary intake leading to many more hypotheses than concrete mechanisms. Understanding the role of food compounds in aging will serve as the basis for dietary recommendations made to older adults through nutritional interventions.


Aging and AMD


Dietary practices throughout the lifespan influence health and well-being in midlife and older adulthood for a variety of diseases (e.g. CVD, cancer, diabetes), yet little is known about the role of lifelong dietary lutein/zeaxanthin and docosahexaenoic acid (DHA) intakes have on eye health in midlife and older adulthood. Age-related macular degeneration (AMD) is the leading cause of irreversible legal blindness in the US [12]. In addition to genetic susceptibility and age [13], risk factors for AMD include: light-colored irises [14], female sex [15], cigarette smoking [16], a high body mass index (BMI, kg/m²); [17], and low dietary intake of plant pigments called carotenoids [18, 19] and DHA [20-22]. The number of pregnancies has recently been identified as a risk factor, explained on the basis of loss of maternal DHA, across the placenta for fetal neurodevelopment. Of these risk factors, dietary intake of carotenoids and DHA is likely the most readily modifiable. Carotenoids and DHA are important structural and functional components of the eye. The macular pigment is composed of lutein and zeaxanthin, which helps protect the macula by filtering blue light, protecting against photoreceptor damage [18]. DHA is concentrated in the photoreceptors and it protects against inflammation, oxidation, ischemia [20-22]. Thus, both dietary lutein/zeaxanthin and DHA are important to healthy vision and dietary habits throughout life are likely important to prevention of AMD. We will test the hypotheses that: 1) increased BMI earlier in life (late teens and early 20s) is associated with decreased macular pigment optical density (MPOD) and 2) increased dietary intake of DHA increases MPOD. This information will be the foundation for future studies to examine if/how early dietary habits protect against AMD in later years.


Understanding the Role of Folate in Health Promotion


The mandatory folic acid fortification policy implemented in 1998 in the US has led to a significant increase in population circulating blood folate level. Folic acid, which is more effectively absorbed than naturally occurring folate in food, was added to grain products and is present in supplements. Dietary supplements and cereal consumption are prevalent among older adults, raising concern about consumption of total folate (folic acid and food folate) above the tolerable upper intake levels of 1000 micrograms. High total folate intake has resulted in the appearance of unmetabolized folic acid (UMFA) in blood circulation. UMFA is now quite prevalent and was detected in approximately 40% of adults aged 60+ years [23]. To date, little is known about the health effects of chronic exposure to UMFA in older adults; but high folate intake and potentially UMFA may contribute to chronic disease outcomes [24]. Folate might pose dual effect on carcinogenesis via its role in DNA synthesis, methylation and repair, adequate folate intake may prevent the development of precancerous lesions; excessive folate intake, through high-dose folic acid supplements or supplements plus fortified food, may promote carcinogenesis [25]. Additionally, research was conducted to address the question of whether B vitamins play a role in CVD or stroke prevention. Although an inverse relationship between blood folate and CVD and stroke has been observed in several prospective studies [26], longitudinal studies failed to report significant results [27] and clinical trials did not find any beneficiary effect in preventing CVD and stroke with B vitamin supplementation [28]. It is of interest to examine the relationship between high folate intake and CVD and stroke morbidity and mortality in older adults.


STUDY AREA 2: ENVIRONMENTAL ASSESSMENT


Many factors influence older adults eating behaviors [29]. The Social Ecological Model presents not only individual and interpersonal factors but also environmental factors which are sometimes out of older adults direct control. These factors include but are not limited to affordability of healthful foods, accessibility of foods and barriers to purchase or get information about healthful foods, and various places where older adults could purchase, consume, make decision about, and get information about food. These determinants mentioned above are important yet understudied among older adults [29].


Environmental Assessment


Without consistent access to quality, affordable produce items, underserved populations, like older adults, are at increased risk of obesity and other forms of diet-related diseases. People who cannot afford to maintain a balanced diet and/or do not live close to sources of a variety of healthful foods are more likely to become obese and are at higher risk of chronic disease, and thus increase health care costs. Eating healthful foods, including fresh fruits and vegetables, can help maintain weight and prevent weight gain and can reduce the risk of chronic diseases [30].

Better understanding the environment in which older adults live (e.g. urban vs. rural) is important when developing public health policies and lifestyle interventions. Currently there is not an environmental survey specifically targeting older adults for use by community agencies (e.g. Agencies on Aging, Extension, and Public Health). Developing such a tool would support community-based efforts to support successful aging. Our previous NE1039 research utilized a panel of national experts in older adult nutrition, including some from this multistate research group, to identify important and changeable environmental determinants of healthy eating among older adults. Principal enablers of healthy eating included accessibility of healthful foods, affordability of these foods, social support, and living accommodations to address specific health conditions [31]. The panel also identified food stores, restaurants, congregate nutrition sites, religious settings, health care settings and senior housing as important behavioral settings which influence the enablers to different degrees [31]. However, little research has been done from consumers standpoint to show their perceptions on how the environment influences their decisions about food. It is important to do so since the dynamic relationship between consumers and the environment could provide a better basis of understanding eating behaviors and food choices [32]. In order to do so, we need to study which aspects of the environment have more influence on older adults eating behaviors than others based on consumers perceptions. These efforts will take place in MA, NY, WV, and I; providing urban and rural perspectives. Doing so increases the usability of this survey tool in a variety of locales.


Geographic information system (GIS) is one of the most commonly used objective methods to study the environment [33]. GIS is very useful to visually identify the gap between older adults needs and what the current environment offers. GIS studies have described the food environment, identified food deserts, discovered associations between environmental determinants and health outcomes, and identified populations at risk of certain food environment exposures or health outcomes [34-36]. However, more research is needed in the older population to identify environmental features related to aging, to assess the relationship between current food environment and health outcomes of older adults, and to identify older adults in most need of healthful foods. These results can be used to inform the community stakeholders who are considering policy changes to better address the nutritional needs of older adults in their work.


STUDY AREA 3: LIFESTYLE NEEDS ASSESSMENTS AND INTERVENTIONS


Education is critical to increasing the awareness of and knowledge about health promoting behaviors that can reduce the risk of chronic disease and disability, thereby improving ones quality of life. The current economic situation has limited the availability of traditional health and wellness programs for many populations, especially baby boomers and older adults. Creative, transdisciplinary person-centered health and wellness programs and materials offer an opportunity to reduce chronic disease risk and enhance ones quality of life through improved health and well-being. With advancing age and its concomitant decrease in metabolic rate, increase in visceral fat, and decrease in activity comes negative changes in lipid and lipoprotein and oxidative stress and inflammation [37] that herald CHD risk progression [38]. Diets high in fruits and vegetables have been associated with less inflammation [39], oxidative stress [40] and endothelial dysfunction [41] and lower CVD risk [42, 43]. Programs that define the role of weight loss, healthy diet, and exercise are needed in this high-risk group.


For this multistate project, we will assess the nutritional and physical activity needs of midlife and older adults to design and evaluate patient-centered interventions. The resulting interventions may be structured differently depending on the needs of the target audience, but the multistate team members developing and implementing these interventions will work collaboratively in identifying assessment tools to use when collecting outcomes data. The results of this work in community nutrition and health education can be used by other individuals, organizations, and communities to effectively bring about behavior change that promotes health and well-being for older adults. This style of research is challenging because it requires extensive assessment and evaluation and thus may take several years to create an evidence-based program. However, the advantage to this process is that the end result is an effective nutrition and health program available for use by a variety of individuals, organizations and communities.


Physical Inactivity and Cardiometabolic Risk with Rheumatoid Arthritis


Arthritis is the most common cause of disability in the US, affecting 46 million Americans now [44] and expected to increase to 67 million by 2030. Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis [45]. Individuals with RA experience joint destruction, deformity, loss of physical function, increased mortality rates, poor nutritional status, and lower quality of life, largely attributed to pain and fatigue [45-48], and higher morbidity and mortality from CVD compared to the general population [49, 50]. The percentage of obese individuals with RA reflects the trends of the general population [51, 52]. Steroid drugs increase appetite and can lead to weight, and this increased adiposity resulting in more physical limitations, disease activity, and functional disability [53, 54]. We completed a pilot study at NYU examining the relationship between body composition, disease activity, and functional status in adults with RA. Higher body adiposity was associated with greater disease activity and poorer functional status. Historically, individuals with a diagnosis of RA were told to limit physical activity due to a fear that excess exercise might increase disease activity and damage the joints. However, regular physical activity is now recognized as an essential treatment component since recent studies show that regular exercise can improve physical conditioning, strength, mobility, and overall health without having a detrimental impact [55-62]. Unfortunately, those with RA are less likely to be physically active than their general population counterparts [63-66]. In our pilot study, we also examined the relationship between physical inactivity and cardiometabolic risk in adults with RA through the Rheumatology Clinical Research Center at the NYU Center for Musculoskeletal Care. Preliminary data provide compelling support for the relationship between levels of physical inactivity and cardiometabolic risk. We plan to develop a behavior-based nutrition and physical activity intervention for adults with rheumatoid arthritis from ethnically and socioeconomically diverse populations.


Community-Based Nutrition and Physical Activity Interventions


Previous University of Rhode Island (URI) research has built a foundation for expanding the outreach efforts to reduce obesity and CVD risk factors and increase physical activity and functioning in at-risk older adults [67-70]. The objectives of the URI Dietary Education and Active Lifestyle (UR-IDEAL) studies have been to implement diet and exercise interventions to improve basic science, improve community health and to train students in transdiciplinary research. The first UR-IDEAL study was a randomized clinical trial that showed significantly greater weight loss and fat mass loss in participants who completed the combined resistance training and dietary intervention [68]. When the diet and resistance training program was implemented in four Rhode Island senior centers, there were significant improvements in dietary quality [67] and physical functioning along with significant weight loss [70]. Since older adults can have a difficult time with some traditional exercises, an alternative exercise was tested for impact on similar outcomes. The third study of UR-IDEAL tested the addition of Tai Chi, a low-impact, moderate intensity activity to a behaviorally-based dietary intervention. A similar design was used in that a randomized clinical trial was performed first to see the efficacy of the intervention and then the combined program, Tai Chi and dietary modifications was completed at two senior centers. Just recently, another phase of the UR-IDEAL study was completed in an urban senior center with more than 60% of the participants being minorities. Instead of looking at one exercise modality, the participants completed Tai Chi and resistance training in addition to the behaviorally-based dietary intervention.


The research conducted by Iowa State University (ISU) is serving as the foundation for future community-based interventions through Extension, the states public health and aging departments. Statewide focus groups and nutritional assessments have revealed a need and preference for wellness programming targeting fitness, nutrition and financial well-being [71]. Screening of nutritional risk is critical in order to help at risk older adults receive early treatment to prevent the development of the malnutrition. Malnutrition is still a concern, despite increasing rates of overweight and obesity in midlife and older adulthood as overweight and obese older adults can become malnourished as a result of reduced physical activity and the consumption of an energy-rich, nutrient-poor diet [72]. Nutritional screenings of community-residing older Iowans (N=319) using the Mini Nutritional Assessment [73, 74] found that 23% of those screened were at risk or malnourished. One of the main identified risk factors was limited meal intake. These assessments support the need for lifestyle interventions. The interventions developed and evaluated to date have led to health-promoting behavior change. A newsletter-based, paraprofessional-led nutrition education program conducted for congregate meal participants significantly reduced nutritional risk, increased vegetable and dairy intake frequency [75]. A 3-week whole grains education program for adults age 60+, developed as part of this multistate team, is currently being implemented and evaluated through Extension in Iowa and New Hampshire. Preliminary results indicate it is leading to significant improvement in knowledge about whole grain selection. Finally, the Living (well through) Intergenerational Fitness and Exercise (LIFE) program, a 25-week exergaming physical activity program for older adults resulted in significant improvement in physical activity participation [76], subjective well-being [76], and functional fitness [77].


Within the area of community-based nutrition education programming, there is increasing interest in exploring the effectiveness of gardening with dietary outcomes. Research addressing fruit and vegetable consumption among low-income populations often focuses on individual-level barriers, such as cost, inadequate time for preparation [78], poor knowledge of nutrition [79], and limited cooking skills [80]. However, focusing on individual-level barriers may obscure the role that community-level barriers, such as the food environment, may play in the socioeconomic disparities in both diet and obesity [81, 82]. This project will investigate the role of demand-side barriers in impeding access to the food and the main causes of food insecurity. The data gathered by conducting the focus groups sessions will be used to develop hands-on training in encouraging the development of vertical or indoor gardening to grow vegetables, hosting nutrition education and food demonstrations to community groups in schools, churches and housing complexes and developing simple physical activities to reduce obesity and diabetes that were used in the ISU LIFE [83] and the UR-IDEAL projects [70]. The nutritional status of the participants will be assessed with the DST [84], which is being used by four other sites involved in this multistate project.


Need for Multistate, Cooperative Work for Success


The multistate team for this project has a long and successful collaborative history of research that explores the impact of dietary modifications on the health status throughout the life cycle [31, 67, 68, 83, 85-87]. This team identified that the increase in the midlife and older adult population, the lack of evidence-based research and concurrent stresses on the public health care system created the perfect storm. Within the last 6 years, experts in physical activity, physical functioning, and Extension joined to provide a more holistic approach to improving the health of older adults. To continue to increase our ability to examine this more holistic view of aging successfully, we recently added investigators who do more basic and mechanistic research to provide a better understand of the aging process at the molecular level and to investigate how dietary and physical activity modifications impact those molecular changes in vivo. The increased locations and populations enhance the generalizability compared to individual researchers or single institutions. The USDAs support is evidenced by its continued funding of nutrition and physical activity interventions for older adults. In addition, the NIH recognizes the complexity of health care issues and the critical need for transdisciplinary work on these issues via its Interdisciplinary Research Program in their Office of Strategic Organization.