Characterization of Macroph-aging: the Role of GILZ (Glucocortioid-Induced Leucin Zipper)

• Applicant: Professorin Dr. Alexandra K. Kiemer
• Subject Area: Pharmacology ; Immunology ; Pharmacy
• Term: from 2010 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 163639620

Aging is characterized by chronic inflammatory processes. Macrophages as innate immune cells distinctly contribute to this permanent inflammation. Our own data show that the protein GILZ (glucocorticoid-induced leucine zipper) regulates the activation of mouse macrophages obtained from young mice: an acute decrease in GILZ levels amplifies the defense readiness of macrophages. On the other hand, increasing GILZ levels contribute to the resolution of inflammation and to the re-establishment of a resting state.In immune cells from aged animals we observed decreased GILZ levels, which go along with an elevated immune response. At the same time we could show that inflammatory processes as well as the presence or absence of macrophages induce epigenetic changes in these tissues. Epigenetic changes have increasingly been recognized as important characteristics of aging processes.Based on this knowledge the following hypotheses will be tested within this project:(I) Chronic age-dependent inflammatory reactions are based on reduced GILZ levels. Attenuated GILZ impairs the resolution of inflammation, which are normally due to tolerization phenomena.(II) The age-dependent decrease of GILZ levels is induced by an altered glucocorticoid metabolism.(III) Macrophages themselves show signs of senescence and promote aging phenomena in the tissues, in which they reside. The hypotheses will be tested in tissue cultures, in mouse in vivo investigations, as well as in experiments on human lung macrophages. For the first time this project aims to decipher the epigenetic aging of macrophages from mice and humans via next generation sequencing techniques.The project will deliver fundamental knowledge on aging phenoma in macrophages and how these contribute to aging processes of the whole organism.

• DFG Programme: Research Grants