Scientists in Germany have discovered a way to dramatically reverse the molecular age of human cells. By reprogramming blood cell precursors from an 80-year-old, they created neural stem cells with molecular age characteristics similar to those of a person younger than 20.

How blood cells were transformed into neural stem cells

Researchers from University Hospital Bonn, the University of Bonn and RWTH Aachen University reprogrammed immature red blood cell progenitors directly into neural stem cells. These cells 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 previous approaches, this rejuvenation occurred gradually. That allowed the researchers to track cellular changes over an extended period and investigate how biological age can be reversed.

The study was published in the journal Aging Cell.

How scientists reprogram blood cells into brain stem cells

The human body contains hundreds of specialized cell types. All of them originate from a single fertilized egg and carry essentially the same genetic instructions. As cells develop, however, they acquire specific identities and functions. Under normal circumstances, skin cells do not transform into liver cells, and blood cells do not become nerve cells.

Modern experimental techniques can overcome some of these biological limitations. Scientists can reprogram certain mature or immature cells so they acquire entirely different identities. For example, cells can be converted into neural stem cells capable of generating neural tissue. This approach could eventually support research into neurodegenerative diseases.

The process relies on proteins called transcription factors. These proteins control gene activation and alter the genetic instructions a cell follows, changing its developmental pathway and giving it a new cellular identity.

“Using this method, we directly converted red blood cell progenitor cells into neural stem cells,” explains Professor Oliver Brüssl, director of the Institute of Regenerative Neurobiology at Bonn University Hospital.

Previous experiments by the Bonn team showed that neurons created through this approach could successfully connect with existing neurons after being transplanted into mouse brains.

Reprogramming reversed more than 60 years of cellular aging

The latest research examined a notable outcome of cellular reprogramming: a substantial reversal of molecular aging.

“In our current study, however, we focused on a different phenomenon: the observation that cells become significantly younger during reprogramming,” says Professor Brüssl, who is also a member of the Interdisciplinary Research Area Life & Health at the University of Bonn.

To measure the change, the researchers examined the cells’ molecular clocks, including biological markers known as the epigenetic clock. These clocks estimate a cell’s biological age by analyzing chemical modifications to DNA that change as organisms age.

These modifications do not alter the DNA sequence itself. Instead, they influence how frequently particular genetic instructions are used, a process known as epigenetic regulation. Because these patterns change in predictable ways over time, researchers can use them to estimate a cell’s molecular age.

The results showed that cells taken from an 80-year-old developed molecular age signatures comparable to those of a person younger than 20. In other words, the process reversed more than 60 years of cellular aging at the molecular level.

“We also know that this epigenetic rejuvenation causes cells to actually behave like younger cells,” the scientists say.

A slower rejuvenation process reveals how cells become younger

Scientists have previously observed that cellular reprogramming can reset biological age. However, earlier demonstrations generally relied on a more complex, two-step process.

First, researchers convert cells such as blood cells into pluripotent stem cells. These versatile cells can develop into many different cell types throughout the body.

The pluripotent stem cells are then guided to become neural stem cells, which can produce specialized cells found in the nervous system.

With this traditional approach, rejuvenation happens relatively quickly, making it difficult to observe all the molecular changes involved.

The Bonn researchers avoided the pluripotent stem cell stage altogether.

“In contrast, we converted blood cells directly into neural stem cells without going through the pluripotent cell stage,” said Professor Brüssl. “With our approach, rejuvenation occurred gradually and could be tracked for more than 100 days.”

The researchers observed a dramatic decrease in molecular age. The study highlighted rejuvenation of approximately 60 years after 50 days, while the process continued for a much longer period. This extended timeline allowed scientists to examine how biological changes develop instead of observing only the final result.

What cellular rejuvenation could mean for Alzheimer’s research

The ability to watch cells gradually become younger could help researchers understand the mechanisms that control biological aging.

By studying this process, scientists can investigate which molecular pathways are involved and test whether specific substances speed up or slow down cellular rejuvenation.

“Such long-term rejuvenation is ideal as an experimental model. Because the epigenetic clock resets slowly over several weeks, we can use this model to investigate which factors or active substances accelerate or slow down the rejuvenation process.”

The finding may be particularly relevant to neuroscience, where aging is closely linked to the development of serious neurological conditions. However, the study does not establish a treatment capable of reversing human aging. Instead, it provides a laboratory model for investigating how cells regain youthful molecular characteristics.

This model could ultimately help scientists better understand the cellular changes associated with conditions such as Alzheimer’s disease.

“After all, the most important risk factor for neurodegenerative diseases such as Alzheimer’s disease is age!”

The study involved teams from Bonn University Hospital, the University of Bonn and RWTH Aachen University. Funding was provided by the EU’s Horizon 2020 programme, the German Research Foundation (DFG) and the Federal Ministry for Research, Technology and Space (BMFRT).