Scientists have long known how to make cells younger—at least in the sense that adult cells can be converted into pluripotent stem cells very similar to those found in embryos. While this capability has been foundational for biological research, these methods aren’t viable for anti-aging technologies, for a few reasons.
“You don’t want to have a pluripotent cell in your body, because it can become all types of cells,” says Oliver Brüstle, a professor who studies stem cells at Germany’s Bonn University.
Additionally, the few key genes involved in the stem cell conversion process can drive the formation of cancer if left active. That’s why Brüstle and his team have looked for other ways of de-aging cells without going through a pluripotent state. In their recent study published in Aging Cell, the researchers started with blood cells from people of various ages, including an infant and a 101-year-old donor.
They guided these cells into a younger state but not all the way toward becoming embryonic-like stem cells. And as this transformation progressed, the chemical signals in the DNA that help estimate a cell’s age also changed. In less than two months of reprogramming, one biomarker in particular was set back as far as 60 years.
Aging continued to reverse even when the scientists drastically reduced the cells’ ability to multiply. Therefore, the apparent rejuvenation can’t be explained solely by the fact that the cells were dividing and producing new cells over and over again. However, the mechanism that did erase these signs of aging is still unclear.
“The hope is that you actually can do this systemically in the entire animal,” Brüstle says. “But if you think about applying it in a patient, then you want to be sure this is not a lab experiment, so it’s about finding the mechanism.”
The researchers also shifted the blood cells specifically into a kind of cell that produces neurons. One caveat is that blood cells and neurons age on different timelines, so the extent of the reversal could be exaggerated by the use of a different measuring stick. The authors acknowledge this limitation in their paper, though this discrepancy couldn’t account for all the age-associated biomarkers that reversed course.
Blood cells getting brainy also would not be a desirable result if you gave a patient a de-aging drug, but it would be useful for other regenerative medicine purposes. However, what Brüstle sees as one of the most exciting outcomes of the study is the information gleaned about the process of de-aging.
Usually, making stem cells is quick. That’s useful for many experiments, but it doesn’t give researchers the chance to study cells as they shed the markers of age. In this recent study, since the scientists were able to slowly turn back the cells’ biological clocks, they could track each step of de-aging. “Now we can actually try to dissect the process much more easily than having an instantaneous event,” Brüstle says.
Scientists began converting adult cells back into stem cells two decades ago, but we’ve known very little about how the subsequent de-aging occurs. This means when clinical researchers test potential medical interventions for age-related conditions, they haven’t always had a reliable measure to compare against.
“Now we have a model” Brüstle says. “You can work along this, and now you can probe a zillion things. What impacts the process? This will lead you to the mechanisms. That’s our hope.”
Additional reporting from Anna Rogers.
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