Scientists in Germany have found a way to dramatically reverse the molecular age of human cells, transforming blood cells from an 80-year-old person into stem cells with an age signature of less than 20 years.
Researchers at the University Hospital of Bonn and the University of Bonn achieved this remarkable transformation by reprogramming immature red blood cells into neural stem cells, which can eventually develop into brain cells. During the process, molecular markers associated with aging were effectively reset, making the cells more than 60 years younger at the molecular level.
Unlike earlier approaches, the rejuvenation happened gradually, allowing scientists to follow the changes over an extended period. This slower process could provide important clues about how cellular aging can be reversed and potentially help researchers investigate treatments for diseases associated with aging.
The findings were published in the journal Aging Cell.
How Scientists Turn Blood Cells Into Brain Stem Cells
The human body contains hundreds of specialized cell types, all of which originate from a single fertilized egg and carry essentially the same genetic instructions. As cells develop, however, they take on specific roles. Under normal circumstances, a skin cell cannot transform into a liver cell, and a blood cell cannot become a nerve cell.
Modern laboratory techniques have made it possible to overcome these biological restrictions. Scientists can now reprogram certain mature cells to adopt entirely different identities. For example, skin cells can be converted into cells capable of producing nerve tissue, an approach that could eventually contribute to treatments for neurodegenerative diseases.
The process relies on a combination of proteins called transcription factors, which regulate how genes are activated. By changing which genetic instructions a cell follows, these proteins can redirect its development and give it a new cellular identity.
“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.
Earlier experiments by the Bonn team had already demonstrated that nerve cells generated through this approach could successfully connect with existing neurons after being transplanted into the brains of mice.
Scientists Reverse More Than 60 Years of Cellular Aging
The latest investigation focused on an especially intriguing consequence of cellular reprogramming: the dramatic reversal of molecular aging.
“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 determine how much the cells had rejuvenated, the researchers examined their molecular clocks, particularly biological markers known as epigenetic clocks. These clocks estimate a cell’s biological age by analyzing chemical modifications to DNA that tend to accumulate or change as organisms grow older.
Importantly, these modifications do not alter the DNA sequence itself. Instead, they affect how frequently certain genetic instructions are used (epigenetics). Because these patterns change predictably with age, scientists can use them to estimate how old a cell appears at the molecular level.
The results were striking. After reprogramming, cells taken from an 80-year-old individual displayed molecular age signatures corresponding to someone younger than 20. In other words, the process had reversed more than six decades of cellular aging.
“We also know that this epigenetic rejuvenation ensures that the cells actually behave like young cells,” says the scientist.
A Slower Rejuvenation Process Reveals New Clues
Scientists have previously observed that reprogramming cells can reset their biological age. However, earlier demonstrations of this effect involved a more complicated process requiring two distinct stages.
First, researchers would convert an existing cell, such as a blood cell, into a pluripotent stem cell. These versatile cells have nearly unlimited developmental “career paths” because they can give rise to many different cell types throughout the body.
The pluripotent stem cell would then be guided into becoming a neural stem cell, which is more specialized and can produce cells found in the nervous system.
This conventional approach produces rejuvenation relatively quickly, making it difficult to examine all the changes taking place.
The Bonn researchers instead bypassed the pluripotent stage entirely.
“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.”
The researchers observed a dramatic reduction in molecular age, with the study highlighting rejuvenation of approximately 60 years after 50 days. Because the process continued over a much longer period, scientists could examine the biological changes as they unfolded rather than observing only the final result.
What Cellular Rejuvenation Could Mean for Alzheimer’s Research
The ability to watch cells gradually become younger could be particularly valuable for scientists trying to understand the mechanisms that control biological aging.
By studying this extended transformation, researchers can investigate which molecular pathways are involved and test whether particular substances can speed up or slow down the rejuvenation process.
“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.”
The findings could be especially relevant to neuroscience, where aging is closely connected to the development of serious neurological conditions. Although the work does not establish a treatment capable of reversing aging in people, it offers a laboratory model for investigating how cells regain youthful characteristics.
This could eventually help scientists better understand the cellular changes associated with conditions such as Alzheimer’s disease.
“After all, age is the most important risk factor for neurodegenerative diseases such as Alzheimer’s!”
The research involved teams from the University Hospital of Bonn, the University of Bonn, and RWTH Aachen University. Funding was provided by the EU’s Horizon 2020 program, the German Research Foundation (DFG), and the Federal Ministry of Research, Technology, and Space (BMFRT).
