While the research is still in its early stages, the team believes that their novel technique can have implications for regenerative medicine and can even cells that are better at healing wounds.
"Our results represent a big step forward in our understanding of cell reprogramming," postdoctoral researcher Diljeet Gill, who conducted the work as a Ph.D. student, said in a statement.
"We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of aging indicators in genes associated with diseases is particularly promising for the future of this work."
Giving skin cells a ‘time jump’
The team says that in experiments that simulated a skin wound, they found that the partially rejuvenated cells showed signs of behaving more like youthful cells.
As we age, our cells' ability to function declines, and the genome collects marks of aging. Regenerative biology’s primary aim is to repair or replace cells, including old ones. According to researchers, one of the most crucial tools in regenerative biology is the ability to create induced stem cells. This involves erasing some of the markers that make a cell specialized.
This new innovative approach solves the problem of entirely erasing cell identity by halting reprogramming partway through the process, allowing the scientists to make the cells biologically younger while still letting them regain their specialized function.
The work builds on Shinya Yamanaka’s 2007 Nobel Prize-winning breakthrough technique. He was the first scientist to turn normal cells, which have a specific function, into stem cells with the unique ability to develop into any cell type. The process of fully reprogramming a cell takes about 50 days using four key molecules called call Yamanaka factors by scientists.
This new method, called `maturation phase transient reprogramming`, only goes through this process for 13 days. It essentially halts the process before skin cells forget how to act like “normal” skin cells. But the partial reprogramming helps them to reattain their ability to function like younger cells.
To show that the cells had been rejuvenated, the researchers first examined each cell’s epigenetic clock, which shows age through chemical tags present throughout a person’s genome. Next, they checked the transcriptome - all the gene readouts produced by the cell. The results showed that skin cells were 30 years younger when compared with untreated cells in the experiment.
Genome analysis revealed that the treated cells didn’t just look young but also acted like younger cells. Moreover, the treated skin cells (fibroblasts) produced more collagen, a molecule in the bones, muscles, and blood, which is responsible for healthy joints and skin elasticity, or stretchiness.
The team also tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in a dish. Tests showed that their treated fibroblasts moved into the gap much quicker to repair the damaged area than older cells. This is a promising sign and experts believe that this research could even be used to create cells that are better at healing wounds in the future and also treat age-related diseases like Alzheimer’s.
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