Scientists reprogram old skin cells to regain youthful function

Babraham: Scientists at the Babraham Institute have developed new techniques for rejuvenating skin cells. This technology allows scientists to rewind the cell’s biological clock for about 30 years according to molecular measurements, significantly longer than previous reprogramming methods.

The research results were published in the journal “eLife”.

Scientists have been able to not only partially restore the function of old cells, but also activate the molecular measure of biological age.

As we age, the functional capacity of our cells declines and the genome accumulates traces of aging. Regenerative biology aims to repair or replace cells, including old cells. One of the most important tools in regenerative biology is the ability to create “induced” stem cells.

This process is the result of several steps, each erasing some of the marks that specialize the cell. Theoretically, these stem cells can be of any cell type, but scientists have not yet been able to reliably reproduce the conditions for redifferentiating stem cells into all cell types.

A new method based on the Nobel Prize-winning technology that scientists use to make stem cells overcomes the problem of completely erasing the cell’s identity by stopping reprogramming in the middle of the process. This allowed researchers to find the exact balance of cell reprogramming, making them biologically younger and at the same time regaining specialized cell function.

In 2007, Shinya Yamanaka was the first scientist to transform normal cells with specific functions into stem cells with the special ability to develop into all cell types. The entire process of stem cell reprogramming takes about 50 days using four major molecules called the Yamanaka factor.

A new method called “temporary reprogramming during maturity” exposes cells to Yamanaka factor for only 13 days. At this point, the age-related changes are removed and the cells temporarily lose their identity. Partially reprogrammed cells were given time to grow under normal conditions to observe whether their particular skin cell function was restored. Genome analysis showed that the cells regained the markers characteristic of skin cells (fibroblasts), which was confirmed by observing collagen production in the reprogrammed cells.

To show that the cells have rejuvenated, researchers have looked for changes in the characteristics of aging. Dr. Diljeet Gill, a postdoc in Wolf Reik’s lab at the Institute, where he studied as a PhD student, explains: Aging-related biological changes in human cells. I was able to apply this to my experiments to determine the degree of reprogramming of the new methods achieved. Researchers have examined multiple measures of cell age. The first is an epigenetic clock, where chemical tags present throughout the genome indicate age. The second is the transcriptome, which reads out all the genes produced by the cell. With these two measurements, the reprogrammed cell matched the profile of the cell 30 years younger than the reference dataset.

The potential use of this technology depends not only on the cells looking young, but also on their functioning like young cells. Fibroblasts produce collagen, a molecule found in bones, skin tendons, and ligaments, providing structure to tissues and healing wounds. Rejuvenated fibroblasts produced more collagen protein than control cells that did not undergo the reprogramming process.

Fibroblasts also move to areas that need repair. Researchers tested partially rejuvenated cells by making artificial cuts in the layer of cells in the dish. They found that treated fibroblasts migrated to the gap faster than older cells. This is a promising sign that one day this study could eventually be used to produce cells that excel in wound healing.

In the future, this study may open up other treatment possibilities. Researchers have observed that their method also affects other genes associated with age-related diseases and symptoms. The APBA2 gene associated with Alzheimer’s disease and the MAF gene involved in the development of cataracts both showed changes towards youthful levels of transcription.

The mechanism behind the success of the temporary reprogramming is not yet fully understood and is the next piece of the puzzle to explore. Researchers speculate that important regions of the genome involved in the formation of cellular identities may escape the reprogramming process.

Dirgit concludes: “Our results represent a major step forward in understanding cell reprogramming. We can rejuvenate cells without losing their function, and rejuvenation gives older cells some function. The fact that we also saw a reversal of aging indicators in disease-related genes is particularly promising for the future of this study. ”Epi, who recently moved to lead the Altos Labs Cambridge Institute. Professor Wolf Reik, Group Leader of the Genetics Research Program, said: Ultimately, it may be possible to identify genes that rejuvenate without reprogramming and specifically target them to reduce the effects of aging. This approach has the potential for valuable discoveries that could open up amazing therapeutic horizons. “