Integrative Analysis of the Gut Microbiome’s Role in Immune Aging:

Decline and dysregulation of immune function is a major underlying cause of morbidity and mortality in old age. While many cellular and functional age-associated changes in the immune system have been described, the molecular networks which regulate immune aging have not been elucidated. Furthermore, the causes of many age-related immune dysfunctions such as chronic elevation of inflammatory responses are also not well understood. Despite being one of the most prominent sources of immune stimulation in our body, the relationship between the gut microbiota and immune aging remains relatively unexplored. The composition and structure of the microbiome is known to change with age, including decreases in the phylum Firmicutes and overall diversity, but the mechanisms by which such changes can contribute to the processes of immunosenescence and chronic inflammation is unknown. In this project we are performing an integrative analysis of DNA/RNA sequencing, metabolomics, and flow cytometry measurements of the microbiome and immune system in a cohort of young (18-45) and older (>65) adults to generate a systems-level understanding of the relationship between age-related changes in the gut microbiome and immune aging.