Molecular and cellular characterization of pre-autoimmune effects in liver and plasma induced by aging in mice

Aging represents a significant risk factor for autoimmunity. The development of autoimmune diseases requires the failure of multiple tolerance checkpoints, some of which are vulnerable to the aging immune process. During adulthood, homeostatic T cell proliferation plays a pivotal role in T cell replenishment. However, this process may result in the selection of T cells with heightened affinity for self- or neoantigens. In parallel to these well-described changes in the immune homeostasis, changes in the cellular kinome strongly depend on age and several protein kinases contribute to all processes of aging and senescence. The contribution of age-related kinases to the development of autoimmunity and autoimmune diseases are so far greatly understudied and therefore a key question in my project.To investigate the effect of age-dependent kinome changes on the development of autoimmunity, we housed normal wildtype C57BL/6J mice for either 1 month (“adolescent”), 3 month (“adult”) or 18 months (“old”) under specific pathogen-free (SPF) conditions. My project aims to investigate differences in the liver of these mice.Therefore, different staining of livers will be used to show histologically the invasion of immune-cells and the progress of inflammation and even more severe the genesis of fibrosis in comparison to different age-related kinases. Furthermore, different liver markers in plasma such as triglycerides, liver-enzymes and cyto-/chemokines will be measured and validated with the enzyme-linked immunosorbent assay. The third part of the project will be the validation of already known differences of the kinome in livers of these mice. Therefore,cultured hepatocytes will be used to test out different kinase-inhibitors in order to analyze a possible inhibititory potential on aging.