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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Research Project #436103

Research Project: Nutrition, Immune and Inflammatory Responses, and Related Diseases

Location: Jean Mayer Human Nutrition Research Center On Aging

2023 Annual Report

Objective 1: Determine the effect of nutritional intervention such as vitamin E on immune and inflammatory responses and resistance to infection using appropriate human and animal models. Sub-objective 1A: Establish the effects of vitamin E supplementation on the incidence and severity of human rhinovirus infection in healthy community dwelling older adults. Sub-objective 1B: Understand the mechanistic basis for vitamin E-mediated changes in incidence and severity of common cold. Objective 2: Determine the life-long effect and underlying mechanisms of food components such as fruits and vegetables on life and health span through longitudinal intervention trials using appropriate animal models. Sub-objective 2A: Determine the effect of long term fruit and vegetable consumption on key biological functions, pathologies, and median life span in lean and obese mice. Sub-objective 2B: Determine the underlying mechanism of fruit and vegetable impact on life- and health-span in normal weight and obese mice.

Aging is associated with dysregulation of immune and inflammatory responses, which contribute to higher morbidity and mortality from several infectious and non-infectious chronic diseases associated with aging. Nutritional status, through maintaining healthy metabolic activity, and immune and inflammatory responses, is a key factor in enhancing health- and life-span. Our long-term goal is to determine the underlying mechanisms of age-related immune and inflammatory dysregulation in order to develop nutritional interventions to prevent/reduce these alterations. Objective 1 will determine the impact and underlying mechanisms of vitamin E on human rhinovirus (HRV)-induced infection (common cold) utilizing a double-blind, randomized, placebo-controlled trial in healthy community-dwelling older adults. Efficacy of vitamin E will be assessed following exposure to HRV by disease incidence and severity, viral shedding, anti-viral immune response, oxidative stress, and expression of signature genes. Objective 2 will determine effect of long-term consumption of fruits and vegetables on median life-span and key immune and metabolic functions at different life stages in an animal model (normal weight and obese mice). Both longitudinal and cross-sectional design will be used to gain insight into causaul relationship between increasing fruits and vegetable consumption and promotion of health- and life-span. Mechanistic investigation will focus on inflammation, oxidative stress, sphingolipid (particularly ceramide) metabolism, and gut microbiota. The results generated from these studies will help develop effective nutritional strategies to delay/mitigate age-related diseases leading to increased health- and life-span.

Progress Report
a) Epidemiological studies suggest that increased fruit and vegetable (FV) intake is associated with a reduced risk of cognitive dysfunction. However, causal relationship between FV intake and cognition has not been established. The objective of this study was to investigate the causal effect of long-term FV supplementation in the context of a low-fat or Western-style high-fat diet in mice. Using a 2 × 2 factorial prospective design, male C57BL/6J (5-wk) were randomly assigned to one of four groups (20/group): low-fat control (LF-C, 10% kcal fat), high-fat control (HF-C, 45% kcal fat), and each with 15% of a unique mixture of FV (patent pending) (w/w) (LF-FV and HF-FV). Novel object recognition test (NOR), a cognitive test for measuring exploration, memory, and object recognition, was performed to evaluate mouse cognitive function at 18 months. Compared to the LF-C group, mice fed the HF diet for 18 months performed significantly lower in the NOR test, indicating cognitive impairment in the HF-C group. FV supplementation significantly mitigated the HF diet-induced cognitive impairment. No significant difference was observed between the LF-C mice and the LF-FV mice. This study provides evidence for a causal role of high intake of FV in preventing Western-style high-fat diet-induced cognition impairment in mice. The mechanisms by which FV improves cognitive function is currently under investigation. b) Studies have shown that obesity is associated with impaired immune function and increased risk of infections. High-fat diet-induced obesity is a commonly used animal model for obesity research. However, due to the fact that a high-fat diet itself can affect immune function, it is not clear if the immune impairment is caused by obesity per se or directly by the high-fat content in the diet. Using CD-1 mice, an outbred mice strain that had highly heterogeneous weight gain in response to high-fat feeding, we investigated this issue. CD-1 mice that were fed high-fat or low-fat diets received influenza vaccine before they were infected with influenza virus. We found that CD-1 mice that became obese after high-fat feeding exhibited more severe symptoms of influenza infection compared to those that had normal weight. Our results suggest that obesity, rather than high-fat diet itself, may be responsible for the impaired immunity.


Review Publications
Goktas, Z., Zu, Y., Abbasi, M., Galyean, S., Wu, D., Fan, Z., Wang, S. 2020. Recent advances in nanoencapsulation of phytochemicals to combat obesity and its comorbidities. Journal of Agricultural and Food Chemistry. 68(31):8119-8131.
Lewis, E.D., Wu, D., Meydani, S.N. 2022. Age-associated alterations in immune function and inflammation. Progress in Neuropsychopharmacology & Biological Psychiatry. 118:110576.
Guo, W., Wu, D., Li, L., Ding, S., Meydani, S.N. 2022. Obesity, rather than high fat diet, exacerbates the outcome of influenza virus infection in influenza-sensitized mice. Frontiers in Nutrition.
Zhu, S., Li, X., Song, L., Huang, Y., Xiao, Y., Chu, Q., Kang, Y., Duan, S., Wu, D., Ren, Z. 2021. Stachyose inhibits vancomycin-resistant Enterococcus colonization and affects gut microbiota in mice. Microbial Pathogenesis. 59:105094.
Zu, Y., Zhao, L., Hao, L., Machref, Y., Zabet-Moghaddam, M., Keyel, P.A., Abbasi, M., Wu, D., Dawson, J.A., Zhang, R., Nie, S., Moustaid-Moussa, N., Kolonin, M.G., Daquinag, A.C., Brandi, L., Warraich, I., San Francisco, S.K., Sun, X., Fan, Z., Wang, S. 2021. Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity. Journal of Controlled Release. 333:339-351.
Eggersdorfer, M., Berger, M.M., Calder, P.C., Gombart, A.F., Ho, E., Laviano, A., Meydani, S.N. 2022. Perspective: Role of micronutrients and omega-3 long-chain polyunsaturated fatty acids for immune outcomes of relevance to infections in older adults - a narrative review and call for action. Advances in Nutrition.