Research from the Babraham Institute has developed a new technique for rejuvenating skin cells. This technique has allowed researchers to rewind the cellular biological clock by around 30 years according to molecular measures, significantly longer than previous reprogramming methods. The partially rejuvenated cells showed signs of behaving more like youthful cells in experiments simulating a skin wound.
They developed a method to ‘time jump’ human skin cells by 30 years, turning back the ageing clock for cells without losing their specialized function. They were able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age. While the research is at an early stage of exploration, it could revolutionize regenerative medicine.
As we age, our cells’ ability to function declines and the genome accumulates marks of ageing. Regenerative biology aims to repair or replace cells including old ones. The new method, based on the Nobel Prize winning technique scientists use to make stem cells, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialized cell function.
In 2007, Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into stem cells which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called ‘maturation phase transient reprogramming’, exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions to observe whether their specific skin cell function returned. Analysis showed that cells had regained markers characteristic of skin cells, and this was confirmed by observing collagen production in the reprogrammed cells.
To show that the cells had been rejuvenated, the researchers looked for changes in the hallmarks of ageing. Researchers looked at multiple measures of cellular age. By these measures, the reprogrammed cells matched the profile of cells that were 30 years younger compared to reference data sets. The potential applications of this technique are dependent on the cells not only appearing younger, but functioning like young cells too. In the future, this research may also open up other therapeutic possibilities; the researchers observed that their method also had an effect on other genes linked to age-related diseases and symptoms. The APBA2 gene, associated with Alzheimer’s disease, and the MAF gene with a role in the development of cataracts, both showed changes towards youthful levels of transcription.
The mechanism behind the successful transient reprogramming is not yet fully understood, and is the next piece of the puzzle to explore. These results represent a big step forward in our understanding of cell reprogramming. They proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that they also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.
Professor Wolf Reik, who lead the research, said: “This work has very exciting implications. Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon.” This research, although in early stages, could eventually have implications for regenerative medicine, especially if it can be replicated in other cell types.
To me, this kind of research is exciting because it shows that ageing is not strictly a one way street—the aging process can be reversed. As we have seen elsewhere—such as in jellyfish—it is possible to not only reverse the signs of aging, but aging itself. Is this a power that exists within us? In our very cells? I, for one, believe that we can tap into this ability, potentially, by actively focusing on our goals and trying to align our subconscious mind on solving this problem. Even if not, we could eventually benefit from treatments based on research like this. I am holding out hope.


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