Scientists Reverse the Biological Age of Human Cells, Making Them Younger

Scientists from Bonn and Aachen have achieved a remarkable breakthrough using this approach. They grew young neural stem cells in the laboratory from ordinary blood samples, including those taken from people over 100 years old. Using two genetic switches, they effectively reprogrammed ageing cells within a few weeks, leaving them with almost no molecular signs of ageing.

The findings were reported by a team led by scientist Lea Jessica Berg and stem cell researcher Oliver Brüstle from the Institute of Reconstructive Neurobiology at the University of Bonn in the scientific journal Aging Cell. The study also involved Wolfgang Wagner's research group at RWTH Aachen University, which focuses on ageing research.

Blood samples were donated by 15 people ranging in age from newborns to 101 years old, Euronews reports. The researchers isolated erythroid progenitor cells from the blood and used a harmless virus to introduce two so-called master genes: SOX2 and cMYC. Master genes contain the instructions for proteins that selectively switch other genes on and off, thereby determining a cell's identity and function.

Using just these two switches, the researchers were able to convert blood cells directly into so-called induced neural stem cells. These are cells that can develop into different types of nerve cells. The process did not require an intermediate stage involving embryonic-like cells, which are typically capable of developing into a wide variety of cell types.

After approximately 12 days, the converted cells displayed the characteristic properties of neural stem cells. They could then continue developing in the laboratory. The process produced not only nerve cells but also two important types of brain-supporting cells. These cells support neurons and help ensure that the brain functions properly.

The biological age of the cells was determined using so-called epigenetic clocks. These analyse specific chemical markers on genetic material. The markers change throughout a person's lifetime and can therefore provide an indication of a cell's biological age.

The measured biological age of the original blood cells closely corresponded to the actual ages of their donors. After conversion into neural stem cells, however, the picture was quite different: the newly created stem cells retained, on average, only about 13% of their original donors' biological age. When the cells were cultured in the laboratory for longer, this figure dropped to less than 5%.

This means that the converted cells appeared biologically much younger. For a 101-year-old person, the measurements would mathematically correspond to cells with an age more typical of those of a child. Importantly, however, the cells do not actually turn into children's cells. Rather, the findings suggest that certain biological markers of ageing are erased during the conversion process.

In conventional reprogramming into so-called pluripotent stem cells, the biological clock is completely reset in approximately three weeks. With the method studied here, it took around 50 days for most traces of biological ageing to disappear. This is an advantage for researchers: because the process takes longer, they can observe its individual stages in greater detail and investigate how biological age can be deliberately influenced.

However, epigenetic clocks provide only an approximate indication of how biologically old a cell is. The research team therefore also examined other characteristic signs of ageing. These included changes in the nuclear envelope, which surrounds the genetic material inside a cell's nucleus, as well as the functioning of the cell's waste-disposal system.

This system breaks down damaged or no longer needed cellular components. The researchers also examined mitochondria, which supply cells with energy, potential DNA damage and so-called senescence markers. The latter are indicators of cells that have stopped dividing but may remain metabolically active.

The results showed that researchers found no significant signs of persistent ageing in the converted stem cells from donors aged 87 and 101. Gene activity also became much more similar. Before conversion, young and old blood cells differed in the activity of nearly 1,900 genes. After conversion, differences remained in only about 12 genes.