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,” explains Prof. Dr. Oliver Brüstle, director of the Institute of Reconstructive Neurobiology at the 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 ImmunoSensation3 Cluster of Excellence and 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!”
Sponsorship
Research groups from the University Hospital of Bonn, the University of Bonn, and RWTH Aachen University participated in the study. The study was funded by the EU’s Horizon 2020 program, the German Research Foundation (DFG), and the Federal Ministry of Research, Technology, and Space (BMFRT).
Publication
Berg, L. J., Franzen, J., Buness, A., Konang, R., Sheng, C., Peitz, M., Till, A., Wagner, W., & Brüstle, O. (2026). Protracted Fate Acquisition and Epigenetic De‐Aging During Induced Neural Stem Cell Conversion of Human Blood Cells. Aging Cell, 25(10), e70751. https://doi.org/10.1111/acel.70751
Contact
Prof. Dr. Oliver Brüstle
Institute of Reconstructive Neurobiology
University Hospital of Bonn
Cluster of Excellence ImmunoSensation3
Transdisciplinary Research Area Life & Health
University of Bonn
Tel. +49 228 6885 500
Email: r.neuro@uni-bonn.de
