SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Members who attended in-person: Sarah Francis (ISU), Anna Arthur (U of Kansas Medical Center), Elgloria Harrison (Lehman College), Melissa Ventura-Marra (WVU), Lee Weidauer (SDSU), Jake Eubank (Lehman College), Elmira Asongwed (UDC), Wen-Hsing Cheng (Mississippi State University), Elizabeth McNeill (ISU), Tia Jeffrey (UDC), Phronie Jackson, (UDC). Members attending virtually: Furong Xu (URI), Matt Delmonico (URI), Ingrid Lofgren (URI), Dara LoBuono (Rowan University), Tiffany Johnson-Largent (UDC), Matthew Richardson (UDC), Yuxiang Sun (TX A&M), Martha Belury (Ohio State University), Kathleen Woolf (NYU), Peggy Connolly (…), Kristen Brown Johnson (…), Ellen Gustavson

Accomplishments

Short-term outcomes:

Objective 1: To conduct multidimensional assessments of diet, physical activity and related factors affecting aging adults.

Objective 1 projects:

  • Performed molecular assessment on aging adults as a means to better inform participants’ activities and diet choices.
  • Conducted needs and preference assessments to determine aging adults’ perceptions and recommendations for community environmental supports for a food secure, culturally appropriate and healthy eating environment
  • Conducted a needs assessment among older adults living in Northeast Tennessee to determine needs and preferences for virtual nutrition education to improve nutritional status and reduce food insecurity among older people. Over 100 older adults completed surveys and 15 professionals participated in a focus group as part of the needs assessment. Results from the needs assessment were used to develop Extension curriculum. These needs assessment results also informed a five-day training, reaching 15 nutrition graduate students and dietetic interns and 30 Extension personnel, providing training on topics such as the nutritional needs of older adults, communication skills, and ageism.
  • Examined the cultural, personal and accessibility barriers to dietary intakes and physical activity by aging adults.

Objective 2: To develop, implement and evaluate interventions that preserve or improve health in aging adults living in rural and urban environments.

Objective 2 projects:

  • Conducted qualitative and quantitative research examining nutrition and physical activity related patterns and predictor of healthy aging.
  • Developed theory-based nutrition and physical activity interventions based on identified needs and preferences
  • Discovered that GHS-R expression is elevated in macrophages under high fat diet-feeding and aging, has a profound role inflammation in adipose tissue, liver and brain. Moreover, GHS-R reprograms metabolic pathways to promote pro-inflammatory macrophage polarization, eliciting meta-inflammation in central/peripheral tissues.
  • Promoted SNAP awareness among 7,000 older adults.
  • Provided direct food and health education to 321 older adults which led to a significant increase in familiarity among participants with recommended lifestyle practices. The majority also reported being “very likely” to make the recommended lifestyle behavior after each lesson.
  • Conducted a commodity and supplemental food nutrition education program that reached 4,000 older adults that resulted in participants using the information provided to make food choices (69.3 percent), of participant, applying the budget tips (63.4 percent), and making at least one recipe at home (72.7 ).
  • Using our novel noninvasive technology (exfoliomics), we will integrate and characterize the relationships between dietary fat and fermentable fiber exposure with respect to maintenance of a “healthy gut”, e.g., programmed cell death/cell division, chronic inflammation-related cell-signaling pathways. Results of this controlled clinical intervention will help to translate the current mechanistic knowledge from preclinical animal models to humans and to de-risk and inform approaches for inflammatory bowel disease and cancer prevention. Interrogating the stool exfoliome is a novel, cost-effective, non-invasive approach to studying effects of interventions on the human gut.

Outputs

  • Collectively we trained 26 undergraduate students, 39 graduate students, 9 post-doctoral associates and 30 extension personnel. The skill acquired by theses trainees includes:
    • Quantitative research (e.g., data collection, data entry, analysis
    • Qualitative research
    • Professional writing
    • Laboratory skills
    • Anthropometric measures
    • Nutritional status assessment
    • Dietary intake assessment
    • Education on topics to support nutrition education for older adults (nutritional needs, ageism, etc)
  • Collectively we received 21 grants ($2,302,056 total): 10 federal, 1 state, 3 foundation, 4 university, 1 research station, 2 others.
  • The team published 31 journal articles including 2 joint journal articles (DC, IL, IA, MD, RI, SD, WV) and 10 published abstracts including one joint abstract
  • The team provided 18 research presentations
  • The team supervised the publication of 4 theses and/or dissertations.
  • Measurable benefits to junior non-tenured faculty in establishing their research agendas including publications, interinstitutional collaborations, and election to leadership positions within this project.

Activities

  • Seven states (DC, IL, IA, MD, RI, SD, WV) are actively working on publishing findings from a 2020 collaborative needs assessment study. One paper has been published from that project and five more papers either in review or in preparation.

Milestones:

  • As part of the ACL-funded Socially Nutritious project we completed a needs assessment to inform project development, completed a draft of an Extension curriculum to pilot in late fall 2022, and completed a five day training for graduate students and dietetic interns and Extension personnel.
  • “Aim 1. Determine the roles of myeloid GHS-R in lifespan and healthspan. Study Ghsr-MφKO mice under normal aging (feeding regular diet) and aging obesity (feeding HFD) to determine: 1A) Lifespan: Survival rate by assessing length of survival. 1B) Healthspan: frailty score, cognitive functions, circulating inflammatory cytokine levels and C-creative protein, fecal and plasma metabolites (to assess gut leakiness), glucose tolerance and insulin sensitivity will be evaluated every 6 months throughout lifespan. Aim 2. Determine the effects of myeloid GHS-R on microphage infiltration and polarization in adipose tissue, liver, muscle, pancreas, colon and brain. Young (4- months), middle-aged (12-months) and old (20-months) Ghsr-MφKO and control mice will be subjected to the following studies: 2A) Polarization analysis of peritoneal and tissue macrophages, as well as Bone Marrow Derived Macrophages (BMDM), by flow cytometry. 2B) Metabolic profile by Seahorse extracellular flux to assess M1-promoting anabolic glycolysis and M2-promoting catabolic fatty acid oxidation; 2C) Morphological characterization of tissues by immunofluorescence to detect macrophage quantity and inflammation master regulator NF-kB. 2D) Investigate the effect of aging immunity on genetic aging by assessing telomerase activity in BMDM of old mice.” For the specific aims above, the milestones of next reporting period are as follows: 1. Aim 1: We continue carryover lifespan and healthspan studies.
  • Aim 2: We completed flow cytometry experiments in BMDM and Seahorse analysis in young and middle-aged mice, next period, we will catch up on the aging group. Since the scientific community now emphasizes the need to consider sex as a biological variable, studies need to be conducted in both male and female animals. Most of our data so far are mostly in male mice, a major focus next period is to catch up on female data for on various ages for both aims. Manuscript goals: We aim to submit 3 manuscripts for publication: 1. The role of macrophage GHS-R in high fat diet-induced meta-inflammation to JCI; The role of macrophage GHS-R deficiency on LPS-induced systemic, adipose and hepatic inflammation to Frontiers in immunology.
  • We have translated pre-clinical studies in mouse models of muscle wasting and biologic aging to clinical outcomes in controlled clinical cohorts. Our work with NHANES data analyses has also revealed that adults and children may be a increasing risk for insufficient intake of two essential fatty acids, linoleic and alpha-linolenic acids. Using behavioral methods to assist consumers in identifying foods rich in these two essential fatty acids may be needed to prevent worsened outcomes as people age that are related to mitochondrial dysfunction, muscle loss, cognitive decline and other chronic conditions.
  • Created a Microsoft teams group that houses all NE1939 project related materials including the policy and procedure manual, common assessment tools and corresponding codebooks, and meeting minutes. We disseminated information and findings from this project to nutrition and aging professionals through many publications.
  • We identified the hepatoprotective function of dietary exosome-like nanoparticles in aged mice. Completed a needs-assessment study covering dietary and physical activity preferences and patterns in rural communities.
  • Completion of an NIH R15 grant (Optimized selenium status, gut microbiota, and diabetes; 08.2018-08.2022) Complete health professionals modeling paper and social determinants of health needs assessment paper and submit for publication consideration by end of 2021.
  • Generated strains of C. elegans that can used to mimic the effect of caloric intake on bioenergetic status of animals - optimized an imaging platform for automated measurement of lifespan in C. elegans

Impact of NE1939 related work:

  • To understand the regulation of macrophage reprogramming is very important in combating meta-inflammation relevant to a wide range of chronic diseases in aging. Our preliminary data suggest that GHS-R is a key regulator of macrophage polarization, and suppressing GHS-R in macrophages attenuates inflammation in various tissues and improves insulin sensitivity, thus promoting longer healthspan. GHS-R is an GPCR, which is a highly desirable drug target. Immunotherapy has emerged as one of the most promising intervention in modern medicine. Our novel findings suggest that GHS-R antagonist may serve as a novel immunotherapy for prevention/treatment of obesity-related chronic diseases and aging.
  • Muscle wasting is directly associated with cognitive decline, heart disease and insulin resistance. Our work is elucidating a mechanism that may be shared among these co-morbid diseases. My lab seeks to improve our understanding of the cellular contribution of dysregulated mitochondria in energy imbalance that leads to muscle wasting, cognitive decline, heart disease and insulin resistance. The slowing of these degenerative diseases will increase quality of life, reduce healthcare costs and possibly slow biologic aging so that people can live healthier and longer productive lives.
  • During the past reporting period, over 10,000 older Iowans participated in community education and/or research programs that increased awareness of food security resources, promoted familiarity with healthy lifestyle practices, and assessed program satisfaction and impact. The food security programs resulted in better nutrition choices and better understanding of SNAP.
  • The intended audience during this evaluation period continues to be building the capacity of junior non-tenured faculty on their tenure and promotion trajectory. The direct benefit would be the number of articles published from this data set targeted at physical activity, exercise, diet, and quality of life issues. The impact of their dissemination efforts would provide social, health and environmental benefits to those who interact with older adults thus bridging health policies gaps designed to increase the quality of life for the older urban residing adult. Additionally, assuming roles in the multi-state collaboration assist in the tenure and promotion trajectory.
  • Personalized nutrition was used to assess microbial metabolite phenotype in order to stratify participants and non-invasive host exfoliomics and determine the effects of flaxseed lignan supplementation in a place-bo-controlled crossover trial.
  • An estimation: Up to 3.75% Americans (ca. 12.3 millions) are susceptible to type 2 diabetes due to suboptimal body selenium status at levels 77% of nutritional needs or lower.

Impacts

  1. Aging adults face numerous barriers towards achieving optimal health and wellness including chronic disease, nutritional risk, food insecurity and functional impairments. The United States (U.S.) population is experiencing a shift in demographics, as adults aged 60 to 65 years and older, have become the largest growing age group. The USDA NE-1939 Multistate Project “Improving the Healthspan of Aging Adults Through Diet and Physical Activity” is an interdisciplinary team of researchers who are examining diet and activity factors that influence healthy aging through translational research approaches. Our work addresses the numerous factors impacting the health and well-being of older adults including poverty, food security, nutritional risk, dietary intakes, and physical activity. We examine these issues at a cellular, individual and societal level. Collectively, from 2021 to 2022, we trained 26 undergraduate and 39 graduate students, 9 post-doctoral associates, and 30 Extension personnel. Our team members were awarded 21 grants totaling $2,302,056 for projects conducted as part of this multi-state research project; 10 of which were federal grants. We published 31 journal articles including 2 joint journal article (DC, IL, IA, MD, RI, SD, WV; DC, MD, NY) and 10 published abstracts. We gave 18 research presentations. The impact of these dissemination efforts provides social, health and environmental benefits to those who interact with older adults thus bridging health policies gaps designed to increase the quality of life for the older urban residing adult. Our undergraduate and graduate students benefited directly by working with faculty in conducting research and/or Extension endeavors. Thus, leading to better prepared students for graduate programs, dietetic internships, and the workforce. We developed novel antibody phage display technology that will allow biomarkers for healthy aging to be identified once fully deployed. The work in the area of inflammation will promote the development of targeting dietary therapeutics to slow to prevent the development of muscle atrophy caused by aging, cancer cachexia and other debilitating, inflammatory related conditions. In addition, our food insecurity research found evidence that healthy dietary intake can decrease the risk of functional limitations and mental health issues, such as depression thus providing us with a potential direction to prevent these adverse outcomes among those who are food secure through diet. Further, we completed our nutrition and physical activity needs assessment project which is a collaborative effort across seven states and surveyed 1,200 adults aged 40 years or older to help inform our future intervention work. We have one paper published from this project and five more manuscripts which utilized data from this project either in review or in preparation.

Publications

Please see attachment

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