Location: Jean Mayer Human Nutrition Research Center On Aging
2025 Annual Report
Objectives
Objective 1: Evaluate associations between dietary patterns, food components, and microbial metabolites with nervous system functions and healthspan.
Subobjective 1.A To elucidate associations between vitamins K and D with brain structure (neuropathology and neuroimaging outcomes) and function (cognitive and motor).
Subobjective 1.B: To evaluate vitamin B12 status, cognitive decline, and incident dementia.
Subobjective 1.C: To evaluate vitamin B12 and folate status in preventing AMD and slowing its progression.
Objective 2: Determine the mechanisms whereby dietary interventions attenuate age-related decline of brain and sensory systems.
Subobjective 2.A: Determine the role of diet, aging, gut-retina axis, and glycation on the development of AMD in mice models.
Subobjective 2.B: Determine the impact of bioactive dietary compounds on brain connectivity.
Subobjective 2.C: Evaluate the effects of bioactive dietary compounds on age- and AlzD-impaired neurogenesis.
Subobjective 2.D: Evaluate the effects of nutrients on age-related impairments in brain and sensory function, including cognition throughout the lifespan.
Approach
We aim to define the effects of diet and bioactive dietary compounds on the gradual loss of the functions and structural integrity of the aging brain and sensory system. We will use information available from population-based longitudinal and prospective studies to evaluate associations of diet with nervous system and sensory functions. Diet exposure will be characterized through the assessment of dietary patterns and novel diet biomarkers. Nervous system and sensory functions will be characterized using a combination of measures to capture multiple aspects of brain health. The effects of diet and aging on mechanisms relevant for brain and sensory functions in response to diet and aging will be evaluated across multiple model systems, including rodent models studied across the lifespan. Findings from observational human studies will be used to inform dietary interventions for in vitro and animal studies. This will create a framework for testing nutrient effects, and data from in vitro, animal models, and population-based studies will be translated into proof-of-concept Phase I clinical trials.
The research in this plan integrates with the larger mission of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. The results of the proposed studies will be integrated into the Center’s approach to elucidating nutrition that can improve healthspan.
Progress Report
Our first objective is to evaluate associations between dietary patterns and individual foods on brain and sensory system aging. We received 240 human brain samples from Rush University to study vitamins K and D in three brain regions related to cognition and memory. We also received blood samples obtained prior to death from 170 participants who donated their brain tissue upon death to analyze various vitamin K and vitamin D-related compounds. This will allow us to evaluate the feasibility of using circulating measures of these vitamins as biomarkers of corresponding vitamin concentrations in the brain.
Our second objective is to determine the mechanisms that help dietary interventions slow the rate of age-related decline of the brain and sensory systems. In our work with animal models, we initiated dietary and antibiotic treatments in aged mice. We also bred genetically modified mice for further studies. We created brain slice cultures from mice to study how dietary compounds affect synaptic connectivity and neuroinflammation. We also derived human-induced pluripotent stem cells and evaluated their versatility and potential to differentiate to prepare for follow-up studies.
Accomplishments
1. Low vitamin K intake may impair cognition. There is growing evidence that a healthy diet and its individual components can slow cognitive decline. Many older Americans don't consume enough vitamin K, which is found in produce like spinach, kale, collard greens, and broccoli, as well as soybean oil. ARS-funded scientists in Boston, Massachusetts, found that a long-term low intake of vitamin K in middle-aged mice impaired their cognitive function, reduced their ability to make new neurons, and activated more brain immune cells. These changes may contribute to age-related decline in learning and memory, consistent with findings from previous animal and human observational studies. This study's findings enhance our understanding of how vitamin K might help prevent or weaken cognitive decline in aging.
2. Low glycemic index diet protects the gut microbiome from antibiotics. Oral antibiotics usage can reduce the diversity of the gut microbiome and is associated with increased risk of age-related diseases. Typically, individuals prescribed oral antibiotics are advised to follow a bland, low-fiber diet. However, ARS-funded scientists in Boston, Massachusetts, found that a high glycemic diet combined with antibiotics caused a severe disruption of the gut microbiome, gastrointestinal disease, and sudden death in older mice. Conversely, mice on a low glycemic index diet with high amylose, a prebiotic, experienced less disruption to the gut microbiome and maintained a regular lifespan. The findings suggest that older adults taking oral antibiotics should consume high-fiber, low glycemic index diets to protect their gut microbiomes from the negative effects of antibiotics and to improve health.
3. Intermittent intake of blueberries has similar memory benefits compared to continuous blueberry consumption. Previous studies have shown that daily consumption of blueberries is beneficial, especially for improving memory. However, the ideal intake is unknown. ARS-funded scientists in Boston, Massachusetts, conducted a study on aged male rats to compare continuous versus intermittent consumption of blueberries on brain health. Rats fed blueberries intermittently performed better in fine motor coordination and memory compared to control rats who were not fed blueberries. Inflammation was reduced in both groups who were fed blueberries. These findings suggest that blueberries may not need to be consumed daily to benefit brain health.
Review Publications
Cahoon, D., Fisher, D.R., Zheng, T., Lamon-Fava, S., Wu, D., Rabin, B.M., Shukitt Hale, B. 2025. Dietary blueberry before and/or after exposure to high energy and charge particle radiation attenuates neuroinflammation, oxidative stress, glial cell activation, and memory deficits in rats. Journal of Nutrition. 155(3):690-702. https://doi.org/10.1016/j.tjnut.2025.01.011.
Shukitt Hale, B., Prior, R.L., Burton-Freeman, B. 2024. Polyphenols: With a focus on Flavonoids. In: Tucker, K.L., Duggan, C.P., Jensen, G.L, Peterson, K.E., editors. Modern Nutrition in Health and Disease 12 edition. Jones & Bartlett Learning. P. 511-512.
Zheng, T., Marschall, S., Weinberg, J., Fu, X., Tarr, A., Shukitt Hale, B., Booth, S. 2025. Low vitamin K intake impairs cognition, neurogenesis and elevates neuroinflammation in C57BL/6 mice. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2025.01.023.
Shukitt Hale, B., Fisher, D.R., Cahoon, D.S., Miller, M.G., Carey, A.N., Zheng, T. 2025. Intermittent vs. continuous wild blueberry feeding alters inflammation and behavior in aged rats. Journal of Medicinal Food. https://doi.org/10.1089/jmf.2025.0001.