Age-Related Dysbiosis and Physical Resilience

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This proposal is submitted in response to RFA-AG-20-030 “Microbiome and Aging: Impact on Health and Disease.” The project addresses this RFA by evaluating for the first time the impact of the gut microbiome on physical resilience in mice. Leveraging a multidisciplinary team with extensive experience in both the gut microbiome and aging science, we will address the following specific aims: 1) Determine the extent to which the gut microbiome is connected to age-related declines in physical resilience, 2) Isolate the effects of the aged gut microbiota on resilience responses, and 3) Determine the impact of physical exercise, dietary fiber, and their combination, and associated changes in the microbiome and SCFA functional capacity, on physical resilience in older animals. Resilience will be defined by recovery in physical function, evidenced by a composite set of function measures, and we will also evaluate relationships of the microbiome to purported biologic mediators including insulin sensitivity, gut barrier function, body composition, as well as local gut and systemic inflammation. ANTICIPATED IMPACT: This project will address the Geroscience concept of physical resilience by providing the first data relating resilience to the gut microbiome. This project capitalizes on a history of work by our group and is driven by a conceptual model which posits that age-related changes in gut microbiota drive changes in organism immune function and energy utilization, ultimately contributing to inflammation and body composition changes that impair organismal ability to recover physical function after physiologic challenge. Ultimately this project leverages recent understanding of the importance of the gut microbiome to health and disease and is designed to provide a substantial step toward our long-term goal of advancing understanding of physical resilience to ultimately devise strategies for improving resilience in mid- to late-life.