Bonn researchers successfully rejuvenate human cells in a test tube

Researchers from the University Hospital of Bonn and the University of Bonn have succeeded in dramatically rejuvenating human cells in a test tube. To do so, they directly reprogrammed red blood cell precursors into stem cells from which neurons can be derived. During this process, the molecular clocks that indicate a cell's age were reset. For example, blood cells from an 80-year-old were transformed into stem cells with a molecular age of less than 20 years. Since this rejuvenation process occurred very slowly, it is well-suited for a more detailed investigation of the underlying mechanisms. The results have been published in the journal Aging Cell.

The human body contains hundreds of different cell types. They all originate from the fertilized egg and therefore share the same genetic makeup. However, in the course of their development, they were committed to a specific fate: a skin cell cannot naturally become a liver cell, nor can a blood cell become a nerve cell.

Today, however, it is possible to reverse this determination in the laboratory. For example, nerve tissue can be grown from a skin cell, which may one day be used to treat neurodegenerative diseases. To achieve this reprogramming, researchers use a cocktail of various transcription factors. These factors cause the cell to read different genetic instructions and thus embark on a different developmental path.

Molecular clocks are reset dramatically

Using this method, we have directly converted red blood cell precursors into neural stem cells."

Prof. Dr. Oliver Brüstle, Director, Institute of Reconstructive Neurobiology, University Hospital of Bonn

In previous studies, the Bonn researchers had already shown that nerve cells produced in this way form connections with existing neurons after transplantation into the brains of mice.

"In our current study, however, we focused on a different phenomenon: namely, the observation that cells become significantly rejuvenated during reprogramming," emphasizes Brüstle, who is also a member of the Transdisciplinary Research Area (TRA) Life & Health at the University of Bonn. To measure this, they used molecular clocks. These track DNA modifications that typically occur during aging. These changes do not affect the genetic information itself, but rather the frequency with which this information is read (epigenetics).

The cells' epigenetic clocks were significantly reset by the reprogramming. As a result, cells from an 80-year-old subsequently exhibited a molecular age of less than 20 years. "We also know that this epigenetic rejuvenation ensures that the cells actually behave like young cells," says the scientist.

60 years younger after 50 days

It was already known that a rejuvenation effect can occur during cell reprogramming. However, it had previously only been observed when reprogramming took place in two steps: For example, a blood cell is taken and converted into a pluripotent stem cell, which has virtually all "career paths" in the body open to it. This stem cell is then induced to develop into a neural stem cell, from which only brain cells can emerge.

Rejuvenation occurs very rapidly with this two-step method. "In contrast, we converted blood cells directly into neural stem cells—that is, without first passing through the pluripotent cell stage," said Brüstle. "In our approach, rejuvenation occurred gradually and could be tracked for over 100 days."

This opens up a unique window into a better understanding of cellular rejuvenation processes. "Rejuvenation that extends over such a long period of time is ideal as an experimental model: Since the epigenetic clocks are slowly reset over several weeks, we can use this model to investigate which factors and active substances accelerate or slow down the rejuvenation process."

This is particularly relevant for the field of neuroscience, says Prof. Brüstle: "After all, age is the most important risk factor for neurodegenerative diseases such as Alzheimer's!"