Study provides new insights into age-related brain changes

22.08.2023 14:20

A groundbreaking study published in the journal Nature on August 2, 2023 provides new insights into the aging processes in the brain and possible approaches to combat age-related neurodegenerative diseases. The research team led by Prof. Dr. Andrea Ablasser from the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, conducted the study in collaboration with scientists from the Medical Faculty of the University of Friborg.

The researchers from the Institute of Neuropathology at the University Hospital of Freiburg, together with their Swiss colleagues, showed that the cGAS-STING signaling pathway, which mediates the immune response to DNA, is a decisive factor in chronic immune cell activation and nerve cell loss and functional decline in old age in mice can be. “After using a previously developed, novel drug to block STING, the age-related cellular changes were reduced,” explains the study’s co-author Dr. Marius Schwabenland, scientist at the Institute of Neuropathology at the University Hospital of Freiburg and fellow in the IMM-PACT Clinician Scientist program at the Medical Faculty of the University of Freiburg. “In parallel, there was an improvement in brain function, such as improved learning and memory.”

In the opposite case, the researchers were able to strengthen the cGAS-STING signaling pathway in mice by genetically modifying microglial cells, the phagocytes in the brain. This enhancement alone caused the premature onset of age-related cellular changes and cognitive decline.

Potential for stopping neurodegenerative processes in old age

Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the University Hospital of Freiburg and also co-author of the study, emphasizes the importance of these results: “The research results indicate that the targeted blockade of the cGAS-STING signaling pathway could be a promising approach to neurodegenerative processes to stop in old age. Nevertheless, further investigations must be carried out to understand the full potential of these findings.” The study was carried out as part of the Collaborative Research Center / Transregio 167 “Development, function and potential of myeloid cells in the central nervous system” (NeuroMac), whose spokesman Prinz is.

“This study is a great sign of the international research strength of the University Medical Center Freiburg,” says Prof. Dr. Lutz Hein, Dean of the Medical Faculty of the University of Freiburg and board member of the University Hospital of Freiburg. “It confirms that comprehensive support for young, talented scientists is the right path.”

Original publication

Gulen, MF, Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, VV, Favre, L., Mangeat, B., Kroese, LJ, Krimpenfort, P ., Prinz, M., Ablasser, A. cGAS–STING drives aging-related inflammation and neurodegeneration. Nature (2023). https://doi.org/10.1038/s41586-023-06373-1