Scientists Reverse 60 Years of Cellular Aging in Human Cells

German researchers have found a method to significantly reverse the molecular age of human cells. They transformed blood cells from an 80-year-old into stem cells that appeared less than 20 years old at a molecular level.

At the University Hospital of Bonn and the University of Bonn, scientists reprogrammed immature red blood cells into neural stem cells, capable of developing into brain cells. This process reset aging-associated molecular markers, effectively making the cells over 60 years younger.

Unlike previous methods, this rejuvenation occurred gradually. This extended timeline allows scientists to track the changes, potentially revealing how cellular aging can be reversed and aiding research into age-related diseases.

Turning Blood Cells into Brain Stem Cells

Every specialized cell in the human body originates from a single fertilized egg and shares the same genetic code. Over time, cells differentiate for specific functions. Normally, a skin cell cannot become a liver cell, nor a blood cell a nerve cell.

Modern laboratory techniques now allow scientists to overcome these biological limitations. Mature cells can be reprogrammed to adopt different identities. For instance, skin cells can be converted into cells that produce nerve tissue, a potential avenue for treating neurodegenerative diseases.

This reprogramming uses specific proteins called transcription factors. These regulate gene activation and can redirect a cell's development, giving it a new identity by altering which genetic instructions it follows.

'We directly converted red blood cell precursors into neural stem cells using this method,' explained Prof. Dr. Oliver Brüstle, director of the Institute of Reconstructive Neurobiology at the University Hospital of Bonn.

Previous experiments by the Bonn team showed that nerve cells created this way successfully integrated with existing neurons after being transplanted into mouse brains.

Reversing Over 60 Years of Cellular Aging

The recent study explored a key outcome of this cellular reprogramming: a substantial reversal of molecular aging.

'Our current study focused on a different phenomenon: cells become significantly rejuvenated during reprogramming,' Brüstle noted. He is also part of the Transdisciplinary Research Area (TRA) Life & Health at the University of Bonn.

To measure rejuvenation, researchers examined cellular molecular clocks, specifically epigenetic clocks. These estimate biological age by analyzing chemical modifications to DNA that change with age.

These modifications do not alter the DNA sequence but affect how genes are used (epigenetics). Predictable age-related patterns in these modifications allow scientists to estimate a cell's molecular age.

The results were significant. After reprogramming, cells from an 80-year-old individual showed molecular age markers consistent with someone under 20, indicating a reversal of over six decades of cellular aging.

'We also confirmed that this epigenetic rejuvenation makes the cells behave like young cells,' the scientist stated.

A Gradual Rejuvenation Process Offers New Insights

Scientists had previously observed age reversal in reprogrammed cells, but earlier demonstrations involved a more complex, two-stage process.

Typically, a cell like a blood cell would first be converted into a pluripotent stem cell—a versatile cell type capable of differentiating into many different cell types.

Then, this pluripotent stem cell would be guided to become a neural stem cell, a more specialized cell for the nervous system.

This conventional approach rejuvenates cells quickly, making it hard to study all the intermediate changes.

The Bonn researchers bypassed the pluripotent stage.

'Instead, we converted blood cells directly into neural stem cells, without first going through the pluripotent stage,' Brüstle said. 'Our method allowed rejuvenation to occur gradually, trackable for over 100 days.'

Researchers observed a significant reduction in molecular age, with the study reporting approximately 60 years of rejuvenation after 50 days. The extended process allowed for the examination of biological changes as they unfolded, rather than just the final outcome.

Potential Impact on Alzheimer's Research

The ability to observe cells gradually becoming younger could greatly benefit scientists studying the mechanisms of biological aging.

This extended transformation model enables researchers to investigate involved molecular pathways and test if specific substances can alter the rejuvenation rate.

'Rejuvenation occurring over such an extended period is ideal for an experimental model. Because the epigenetic clocks reset slowly over several weeks, we can use this model to investigate factors and active substances that accelerate or slow down the rejuvenation process.'

These findings are particularly relevant to neuroscience, where aging is closely linked to serious neurological conditions. While this research does not offer a treatment to reverse aging in humans, it provides a laboratory model for studying how cells regain youthful characteristics.

This could ultimately help scientists better understand the cellular changes associated with diseases like Alzheimer's.

'After all, age is the primary risk factor for neurodegenerative diseases such as Alzheimer's!'

The research involved collaborations 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).