Mechanism for reducing age-related neuroinflammation

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As we age, our cells lose the ability to effectively eliminate the waste products they produce. This degeneration has serious consequences as it can cause inflammation and dysfunction throughout the body. A team of scientists at the University of Freiburg has now discovered that a specific drug treatment can alleviate this condition by stimulating a mechanism called mitophagy.

Each of our 15 trillion cells produces waste products that need to be recycled like any other waste. The problem is that the efficiency of our intracellular cleansing system, called autophagy, decreases with age. The effects are particularly noticeable in the neurons, where waste products accumulate that can lead to chronic inflammation and neuronal death. A study by Patricia Boya from the University of Freiburg in collaboration with Margarita Salas from the CSIC in Spain investigated whether, despite the ageing process, our cells retain another, more specific type of autophagy, known as mitophagy, which specializes in the maintenance and recycling of mitochondria, the energy power plants of our cells. It is possible that this mechanism could be used to mitigate the harmful effects of the decline in general autophagy.

Improvement of cognitive functions

Using a fluorescent labeling system, the researchers were able to show in mouse populations that mitophagy remained stable or even increased during the aging process, in all organs. ’We suspected that this was a strategy of the cells to prevent the spread of mitochondrial DNA in the cytoplasm. However, it is precisely this spreading that triggers an immune response and thus inflammation,’ explains Patricia Boya. To test this hypothesis, the scientists from the Autophagy Laboratory at the University of Freiburg administered urolithin A, a substance known to stimulate mitophagy, to older mice. ’We wanted to see whether we could use it to stimulate this mechanism and thus artificially encourage the cells to clean up.

Promising results

The rodents that received the drug actually showed lower levels of inflammation at the end of the treatment, which was reflected in an improvement in their cognitive, visual and motor functions. This experiment was successfully replicated in cell cultures from older human donors, indicating that the interspecies phenomenon is maintained at a systemic level. These results suggest that age-related neuroinflammation can be reduced by stimulating mitophagy. This strategy has the advantage that it does not interfere with the physiology of the immune system and does not have an immunosuppressive effect.

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging, Nature Communications