Cambridge scientists have rejuvenated the skin cells of a 53-year-old woman, rewinding the biological clock by 30 years.
In an experiment simulating a skin wound, these cells showed signs of behaving more like those from a 23-year-old, and were quicker than old cells to move in and ‘heal’ the cut.
While the research could lead to new treatments for skin diseases, the hope is to replicate the molecular ‘time-jump’ in cells from other organs.
The real goal is to develop a new generation of therapies for age-related diseases.
As it stands, the experiments appear to have broken a roadblock in regenerative medicine, and perhaps brought us closer to replacing worn-out lungs and hearts with new ones.
That project is still on its infancy. But this is the biggest breakthrough in age-reversal research in fifteen years.
The promise of stem cells
Back in 2007, Japanese stem cell researcher Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into what are known as induced pluripotent stem cells (iPSCs). For this work he was awarded the Nobel Prize in Medicine or Physiology.
Induced pluripotent stem cells, drawn from skin or blood cells, are like a blank slate.
In theory, they have the potential to become any cell type, but scientists have not yet been able “to reliably recreate the conditions to re-differentiate stem cells into all cell types”.
According to a statement from the Babraham Institute, a research partner with Cambridge University, the new method, based on Professor Yamanaka’s technique, “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 specialised cell function”.
What happens with this new method?
The process to reprogram cells from the body into blank-slate stem cells 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, the 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.
Genome analysis showed that “cells had regained markers characteristic of skin cells (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells”.
The significance of fibroblasts
Fibroblasts produce collagen, which is found in bones, skin tendons and ligaments. Collagen molecules help provide structure to tissues and heal wounds.
The rejuvenated fibroblasts “produced more collagen proteins compared to control cells that did not undergo the reprogramming process”.
Fibroblasts are important because they move into areas that need repairing.
The researchers tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in a dish.
The ‘younger’ fibroblasts moved into the gap faster than older cells. The scientists say this is a promising sign that one day this research could eventually be used to create cells that are better at healing wounds.
The mechanism behind the successful transient reprogramming is not yet fully understood, and is the next piece of the puzzle to explore.
Dr Diljeet Gill, who conducted the work as a PhD student, said:
“Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”
He said the research proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells.