Anti-Aging for the brain? A recent study provides new insights into age-related changes in the brain

Important signalling pathway in brain aging identified

09-Aug-2023 - Germany

A landmark study published on 2^nd August 2023 in the journal Nature provides new insights into aging processes in the brain and potential targets for combating age-related neurodegenerative diseases. The research team, led by Prof. Andrea Ablasser from the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, conducted the study in collaboration with scientists from the Faculty of Medicine at the University of Freiburg.

Novel drug reverses age-related changes

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

In the reverse case, the researchers were able to amplify the cGAS-STING signalling pathway in mice using a genetic modification in microglial cells, the scavenger cells in the brain. This amplification alone caused the premature onset of age-related cellular changes and cognitive decline.

Potential for halting neurodegenerative processes in old age

Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the Medical Center - University of Freiburg and also co-author of the study, emphasises the importance of these findings: “The research results suggest that targeted blockade of the cGAS-STING pathway could be a promising approach to stop neurodegenerative processes in old age. However, further investigation is needed to understand the full potential of these findings.” The study was conducted as part of the Collaborative Research Centre/Transregio 167 “Development, function and potential of myeloid cells in the central nervous system” (NeuroMac), for which Prinz is the spokesperson.

“This study is a great sign as far as the international research prowess of the Medical Center – University of Freiburg is concerned," said Prof. Dr. Lutz Hein, Dean of the Medical Faculty at the University of Freiburg and board member of the Medical Center – University of Freiburg. “It proves that comprehensive support for young, talented scientists is the right approach.”

Original publication

Gulen, M.F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V.V., Favre, L., Mangeat, B., Kroese, L.J., Krimpenfort, P., Prinz, M., Ablasser, A.; "cGAS–STING drives ageing-related inflammation and neurodegeneration."; Nature (2023).

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