Epigenomic disruption of immune cell functions with aging in CC founder strains.
Our research is driven by the following questions: i) are CD8+ T cells the main driver of aging in mice immune system similar to human?; ii) is aging of diverse tissues driven by same or different immune cells?; iii) where are the strain-and sex-specific regulatory elements and do the activity of these elements explain life-and health-span differences between strains and sexes? To address these questions we propose to generate chromatin accessibility and gene expression profiles of immune cells in two Collaborative Cross (CC) founder strains with different life-and health-spans: longer living C57BL/6J (B6) and shorter living NZO/HILtJ (NZO).
Aim 1. Establish epigenomic signatures of immune aging in mice. We will study multiple hematopoietic tissues (i.e., spleen, bone marrow, and whole blood) from B6 and NZO miceto establish correlates between signatures of human and mice immune system aging. For this we will profile epigenomes and transcriptomes of immune cells from young and old mice and define epigenomic signatures of immune aging in these tissues.
Aim 2. Uncover parallels between human and mice immune system aging. We will compare epigenomic signatures obtained from human and mice (Aim 1) to establish similarities and differences. We will identify genes, regulatory elements (i.e., enhancers), pathways that are affected with aging in both species using our data analyses pipelines. This work will uncover biomarkers of immunosenescence conserved between species.