Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-51000-090-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jan 23, 2014
End Date: Jan 22, 2019
Objective:
LAB NAME: Nutritional Immunology
1: Determine the impact and underlying mechanisms of obesity during pregnancy on newborn's life-long immune and inflammatory responses and resistance to infectious diseases in appropriate animal models.
1A. To investigate the impact of maternal obesity on immune function and influenza infection in young offspring.
1B. To determine the role of inflammatory, oxidative stress, and selected epigenetic markers that are critical for immune response to influenza and the higher susceptibility of obese mothers’ offspring to influenza infection.
1C. To determine the impact of maternal obesity on immune function and resistance to infection through the life cycle.
2: Determine the effect and mechanisms of food components such as fruits and vegetables or whole grains influence on, and their interaction with, age on immune and inflammatory responses and related diseases in both animal models and human studies.
2A: To determine the impact of increased consumption of F&V on prevention of key age-related biologic dysfunctions and pathologies in a suitable animal model.
2B: To determine the effect of consumption of an isocaloric diet rich in whole grains (WG)[compared to refined grains (RG)] on gut microbiota, and immune and inflammatory responses.
3: Determine the effect of novel forms of iron on systemic and gut immune function, inflammation, oxidative stress.
Approach:
LAB NAME: Nutritional Immunology
Aging is associated with dysregulation of immune and inflammatory responses, which contribute to several age-related diseases. Nutritional status including that during early life has been linked to health status of older adults, and nutritional interventions during different life stages including those during pregnancy are reported to have long-lasting effects on the health status of newborns. Our long-term goal is to determine the underlying mechanisms of age-related immune and inflammatory dysregulation in order to develop nutritional interventions, which will prevent/reduce these alterations. Objective 1 will determine the impact and underlying mechanisms of obesity during pregnancy on newborn's life-long immune and inflammatory responses and resistance to infectious diseases. To achieve this, we will use a diet-induced obesity mouse model and determine: 1) effect of maternal obesity on immune function and influenza infection in young offspring, 2) role of inflammatory, oxidative stress, and selected epigenetic markers in altered immune function and susceptibility to infection in offspring born to obese mothers, and 3) impact of maternal obesity on immune function and resistance to infection through the life cycle. Objective 2 will determine the effect and mechanisms of food components such as fruits and vegetables or whole grains influence on, and their interaction with, age on immune and inflammatory responses and related diseases in both animal models and human studies. In Sub-objective 2A, we will use a mouse model to determine whether the dietary supplementation with a variety of fruits and vegetables would impact health- and life-span through modulating oxidative stress, inflammation and the regulatory lipid, ceramide. In Sub-objective 2B, we will conduct a dietary intervention trial in healthy middle-aged human participants to determine the effect of consumption of an isocaloric diet rich in whole grains compared to refined grains on gut microbiota, and immune and inflammatory responses. These studies will help develop effective strategies to improve health- and life-span of the aged through optimization of immune and inflammatory responses. In Objective 3, we will compare two novel sources of iron, ie., hydroxide adipate tartrate (IHAT, a nanoparticulate form) and Aspiron (a fungal form), with the most commonly used form (ferrous sulfate) for iron utilization and side effects. The outcome variables to be determined include iron status, systemic and gut-associated immune function, inflammation, and oxidative stress, gut microbiota and short-chain fatty acids, ex vivo bacterial proliferation and malarial growth.
