The more we age, the less our cells are capable of “cleaning out” the waste they produce. The consequences of this degeneration are serious since it can cause inflammation and dysfunction throughout the body. A team of scientists at the University of Fribourg has recently shown that treatment using specific drugs can counteract this process by stimulating a mechanism called mitophagy.

Each of the trillions of cells making up our bodies produces waste which, like any bit of rubbish, has to be recycled. The problem is that the efficiency of our intracellular waste-removal system, called autophagy, decreases with age. The consequences of this decline are especially hard on our neurons, where these cellular waste products accumulate, triggering chronic inflammation and eventually leading to the death of brain cells. A study conducted by Prof. Patricia Boya of UniFri in collaboration with the Margarita Salas Center for Biological Research (CIB-CSIC) Spain, sought to verify if our cells, despite aging, preserve another and more specific type of autophagy called mitophagy. The latter mechanism is specialized in maintaining and recycling mitochondria, which are essentially the power stations of our cells. If so, mitophagy could be used to reduce the harmful effects of the decline that affects overall autophagy in the body.

Improvement in cognitive functions
Carrying out studies on mice populations, the scientists were able to show, with the help of a fluorescent imaging procedure, that mitophagy remained stable or even increased during aging. This held for all organs, moreover. “We thought it was a cellular strategy to stop the spread of mitochondrial DNA into cytosol, the liquid that fills the interior of the cell,” Prof. Boya explained. “Yet it is precisely this ‘leak’ which triggers a defense reaction and hence inflammation.”

To test this hypothesis, the scientists of the University of Fribourg’s Autophagy Lab administered urolithin A to aging mice, a mitophagy inducer, that is, a substance that is known to set off mitophagy in cells. “We were hoping to see if we could stimulate this mechanism [with urolithin A] and therefore artificially encourage cells to clean house,” Prof. Boya added.

Promising results
And indeed, the oldster rodents that were given the drug showed lower levels of inflammation at the end of the treatment, which meant an improvement in their cognitive, visual and motor functions. The experiment has been successfully replicated in cell cultures from elderly human donors, evidence that the phenomenon may indeed be conserved across species. These results also suggest the possibility of reducing age-associated neuroinflammation by stimulating mitophagy. This strategy offers a significant advantage in that it does not alter the physiology of the immune system and has no immunosuppressive effect.