The human body contains more than 200 major cell types, but all of those different cells (whether blood cells, brain cells, muscle cells, etc.) originate from a single fertilized zygote. In other words, if we delve into the past of any cell, we will see that it was once an undifferentiated stem cell. The trillions of cells that make up the body are not very different from the billions of people that make up human civilization. In a perfect society, children would be free to develop a supportive role that enhances a healthy civilization, and in a similar sense, stem cells also have this differentiating potential, as they can form virtually all cells in the body. Now, a new study led by scientists at the University of Bonn in Germany finds that if red blood cell precursors undergo some “job retraining” (continuing our civilization-focused analogy), then, surprisingly, they can also rewind their molecular clock by more than 60 years. The results of the study were published in the journal Aging Cell. In a previous study from 2024, neurobiologist Oliver Brüstle from the University of Bonn and his team used transcription factors (proteins that activate “on” and “off” switches for gene expression) to create induced neural stem cells (iNSCs) from blood cells and found that they successfully matured inside the organism. However, in this new study, Brüstle wanted to focus more on a strange peculiarity of these cells. “In our current study, however, we focused on a different phenomenon: namely, the observation that cells are significantly rejuvenated during reprogramming,” Brüstle, lead author of the new paper, said in a press release. “We also know that this epigenetic rejuvenation ensures that the cells actually behave like young cells.” Using a molecular clock that tracks DNA modifications closely linked to aging, the new study showed that blood cell precursors from an 80-year-old person had a molecular age of less than 20 years after reprogramming. Typically, these cells are reprogrammed by first converting the cells into pluripotent stem cells and then developing into iNSCs. This time, however, the authors skipped that intermediate step and used a virus to deliver two transcription factors. After 12 days, the precursor blood cells began to resemble iNSCs, and by using DNA methylation and RNA sequencing, the team was able to track the effects of aging on the cell. “In contrast, we convert blood cells directly into neural stem cells, that is, without first passing through the pluripotent cell stage,” Brüstle said in a press release. “In our approach, rejuvenation occurred gradually and could be followed for more than 100 days.” This slow rejuvenation process is key because in the typical two-step process, changes occur very quickly, but this longer period of rejuvenation allows scientists to investigate what exactly drives these changes. Using that benefit, the authors tracked cells getting progressively younger until they reached about 60 years younger in just 50 days. As Science Alert notes, the cells also acted according to their age (juvenile) by showing less mitochondrial toxicity, and their aging occurred even when cell proliferation was inhibited. And it doesn’t take an adventurous imagination to see how converting old cells into young neural cells could have enormous benefits, especially since many neurodegenerative diseases are linked to aging. It may be true that you can’t teach an old dog new tricks, but that long-held maxim doesn’t quite hold up in the cellular world.
