Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-10700-003-000-D
Project Type: In-House Appropriated
Start Date: Mar 12, 2024
End Date: Mar 11, 2029
Objective:
Objective 1: Investigate metabolic and nutritional mechanisms of cellular aging that can be targeted to promote healthy aging and prevent age-related pathology. (NP 107 4A,5A)
Subobjective 1.A: To assess the induction of ferroptosis as a mechanism for senescent cell elimination in mouse models of aging and age-related pathology.
Objective 2: Determine the mechanistic and physiological roles of dietary components in tissues that regulate systemic metabolism such as brown and white adipose tissue, liver, skeletal muscle, immune responses, and their contribution to aging and age-related obesity.
Subobjective 2.A: To determine the role of adipocyte interferon-related factor 8 in the regulation of adipose and systemic metabolism, obesity, and metabolic complications across the lifespan.
Subobjective 2.B: To determine the mechanistic understanding of the health benefits of tomato carotenoid to protect against high refined carbohydrate diet/age-related nonalcoholic fatty liver disease (NAFLD) across the lifespan.
Objective 3: Determine the mechanisms by which diet and/or physical activity regulate the microbiomes and intestinal homeostasis to promote healthy aging and prevent age-associated diseases. (NP 107 4A, 4B, 5A)
Subobjective 3.A: To determine the impact of a high-soluble fiber diet on the gut-muscle axis in older adult humans and in aged mice.
Subobjective 3.B: To determine the effects of different standard rodent chow diets on normative aging processes (gut homeostasis, microbiome function, neurocognition, and host metabolism) in mice.
Approach:
Our goal is to improve the healthspan of individuals. Our approach is to elucidate the metabolic and molecular mechanisms that regulate healthspan. Many of our studies utilize mouse models of aging which will provide the foundation for future clinical studies to facilitate long-lived healthspan.
Our team of researchers for this project will work together and provide synergy in our approach. A significant detrimental consequence of aging is that cells undergo senescence and do not function properly. Elimination of senescent cells has been shown to improve health. In one project, researchers will investigate if induction of a process called ferroptosis in senescent cells can cause removal of these cells and improve health span. A second project investigates the identification of a protein, called interferon regulatory protein 8 (IRF8), expressed in fat cells which is increased in adipocytes and promotes diet-induced obesity and dysregulated glucose metabolism and whether reductions of the expression of IRF8 protects against obesity and improve regulation of glucose metabolism. A third project is investigating whether when the nutrient carotenoids are isolated from tomatoes it can protect against the development of fatty liver disease. Another project is investigating the role of dietary fiber on beneficially modulating the gut microbiota and their effects on regulating skeletal muscle function and health in aging mice and humans. Diet quality plays an important role in mediating host metabolism across the lifespan in humans but is a commonly overlooked experimental factor in rodent diets. Standard rodent diet composition is highly variable, and this may have potential long-term effects on regulating normative aging processes in mice. Here, we aim to determine the effect of three commonly used rodent diets on biological aging processes, including senescence, gut and glucose homeostasis, and neurocognition, in normatively aging mice.
The research proposed is consistent with the research goals of the Jean Mayer USDA Human Nutrition Research Center on Aging. The results of the proposed studies will be integrated into the Center’s approach to elucidating nutrition that can improve healthspan.
