Research Shows African Killifish Paves The Way To New Treatment Of Aging Brain
Researchers at KU Leuven have shown that a treatment with a cocktail of two drugs not only rejuvenates the brains of old killifish, but also protects against future diseases or injuries. The researchers also unraveled the processes underlying cell aging in the brain. Their research, which was published in the journal npj Regenerative Medicine , opens the way to new treatments for neurodegenerative diseases, such as Alzheimer’s disease.
The African turquoise killifish is a colorful, small fish that lives in temporary pools in Africa, which are often only filled with rainwater for four months. During this period, the killifish has to grow and reproduce quickly, accelerating all developmental processes: growth, sexual maturity, and also the aging process. That’s what makes them so interesting to scientists. At four to six months, the killifish goes through the entire life cycle, the fastest of any vertebrate model organism. The aging process of the killifish also resembles that of humans: they turn gray, get a crooked back and suffer from memory loss (dementia).
In Flanders, the Department of Biology of KU Leuven is the only one currently using the killifish as a model organism. The research group focuses specifically on the aging of the brain.
In their latest study, they looked for the underlying mechanisms responsible for the low recovery capacity of old brain cells in the killifish. They found that those brains are subject to cellular senescence. This means that many brain cells are “sick” or “aged” and secrete harmful substances that prevent the normal functioning and recovery of the surrounding brain cells.
“We were able to confirm this with a specific staining that allowed us to visualize these aged cells,” says researcher Jolien Van houcke. “The difference between young and old brains was huge, with the old brain showing a large amount of diseased and aged cells.”
There are medicines that can remove the aging brain cells. This study was the first to apply it to the ancient killifish brain. They received a combination of two drugs, Dasatinib and Quercetin, for one week.
“Even with this short treatment, we were able to remove 30% of the senescent cells, so that less harmful substances were spread in the brain. Not only did we rejuvenate the brain, the recovery capacity of the brain was also improved: the old killifish had more dividing stem cells after treatment that could grow into new nerve cells, something that is necessary for brain repair after an injury or illness,” says Jolien Van houcke .
Dasatinib and Quercetin are two drugs already approved for use in humans. The combination is already being tested in clinical trials. But then it concerns patients who suffer from other diseases that are caused by “aged” cells, in other places in the body, such as kidney damage in diabetic patients.
The KU Leuven study now confirms that this drug combination may also provide a solution for diseases related to the aging brain. Think of dementia in Alzheimer’s or Parkinson’s patients. However, further clinical studies are needed to demonstrate the effects in humans.
“We have now tested a very short treatment,” says Jolien Van houcke. “But we are now wondering whether a longer treatment yields even better results. We are now going to investigate this further in the first instance, with the help of the killi fish.”