A new technique developed by scientists at the Babraham Institute (United Kingdom) has managed to rejuvenate human skin cells, which has resulted in a setback of the cellular biological clock of around 30 years according to molecular measurements. These rejuvenated cells showed signs of behaving like young cells when subjected to experiments simulating skin injury. Although this is a very preliminary study, it could be an important step for regenerative medicine, especially if the test can be replicated in other types of cells.
The researchers, who belong to the Institute’s Epigenetics research program, have managed to partially restore the function of older cells, in addition to rejuvenating molecular measures of biological age. The ability of human cells to function properly declines as we age and our genome accumulates signs of aging. The goal of regenerative biology is to repair or replace cells, including old ones.
Reprogram cells to make them biologically younger
Regenerative biology uses the ability of humans to create ‘induced’ stem cells. These stem cells have the potential to become any cell type, but science has not yet been able to safely recreate the conditions necessary to re-differentiate stem cells into all cell types.
The method developed in the new research, which has been published in the journal eLife, is based on the technique that won the Nobel Prize in 2012 and that scientists use to create stem cells, since it solves the problem of completely erasing identity cellular partially stopping the reprogramming during the process. This allowed the researchers to strike a fine balance between reprogramming cells – making them biologically younger – and their ability to regain their specialized cellular function.
“We have proven that cells can be rejuvenated without losing their function and that rejuvenation seeks to restore some function to old cells”
Shinya Yamanaka was, in 2007, the first scientist to convert normal cells into stem cells that have the specific ability to become any type of cell. It takes about 50 days to fully reprogram stem cells, using four key molecules called Yamanaka factors. The new method, which has been called ‘transient reprogramming of the maturation phase’, exposes cells to Yamanaka factors for just 13 days. At that time the age-related changes are removed and the cells temporarily lose their identity. They then waited a while for the partially reprogrammed cells to grow under normal conditions, and to see if their specific function as skin cells returned. Genome analysis found that the cells had recovered markers characteristic of skin cells (fibroblasts), which was confirmed by looking at collagen production in the reprogrammed cells.
Create cells capable of healing wounds
The researchers analyzed a series of changes in the characteristics of aging to show that the cells had rejuvenated. Among the measures of cell age they looked at the epigenetic clock, where chemical tags present throughout the genome indicate age. Another was the transcriptome, in which you see all the gene readouts produced by the cell. The results obtained confirmed that the treated cells had the same profile as cells 30 years younger.
The potential applications of the new technique depend not only on the cells appearing younger, but also on the fact that they function as young cells do. Fibroblasts produce collagen, which is present in bones, skin, tendons, and ligaments, and helps structure tissues and heal wounds. They found that the rejuvenated fibroblasts produced more collagen proteins than control cells that had undergone the reprogramming process.
The researchers then tested the partially rejuvenated cells by creating an artificial slice in a layer of cells in a dish and found that their treated fibroblasts headed toward the gap faster than older cells. This is a promising sign that this research could one day be used to create cells that are more effective at healing wounds.
Dr Diljeet Gill, a postdoc in Wolf Reik’s lab, said: “Our results represent a major step forward in our understanding of cellular reprogramming. We have proven that cells can be rejuvenated without losing their function and that rejuvenation seeks to restore some function to old cells. The fact that we also saw a reversal of markers of aging in disease-associated genes is particularly promising for the future of this work.”
Professor Wolf Reik, who has led the research, says: “This work has very exciting implications. Eventually, we will be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of aging. This approach promises valuable discoveries that could open an amazing therapeutic horizon.”
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