Scientist Turning Back Clock on Old Skin Cells

Science News -- May 2, 2022: The Babraham Institute's research has devised a mechanism to 'time leap' human skin cells by 30 years, thereby turning back the clock on cells' aging without affecting their specialized function. Researchers in the Institute's Epigenetics research group were able to partially repair the function of aged cells while also revitalizing molecular markers of biological age.

The study was published today in the journal eLife, and while it is still in the early stages of development, it has the potential to revolutionize regenerative medicine.

What is the definition of regenerative medicine?

Our cells' ability to function reduces as we age, and our DNA collects signs of aging. The goal of regenerative biology is to repair or replace cells, especially those that have died. Our ability to make 'induced' stem cells is one of the most essential tools in regenerative biology. The procedure is made up of numerous phases, each of which erases some of the markers that distinguish cells as specialized. These stem cells have the ability to become any cell type in theory, but scientists have yet to be able to reliably reproduce the conditions that allow stem cells to re-differentiate into all cell kinds.

Rewinding the clock

The new procedure, which is based on a Nobel Prize-winning technology for creating stem cells, avoids the difficulty of completely erasing cell identity by pausing the reprogramming process halfway through. Researchers were able to strike the perfect balance between reprogramming cells to make them biologically younger while retaining their specialized cell function.

Shinya Yamanaka was the first scientist to convert normal cells with a specified function into stem cells with the ability to develop into any cell type in 2007. The entire stem cell reprogramming process takes about 50 days and involves four critical molecules known as Yamanaka factors. The new technique, known as'maturation phase transient reprogramming,' involves exposing cells to Yamanaka factors for only 13 days. Age-related alterations have been erased at this point, and the cells have momentarily lost their individuality. The partially reprogrammed cells were allowed to develop in normal settings for a period of time in order to see if their specific skin cell function restored. Genome analysis revealed that the cells had regained skin cell markers (fibroblasts), which was validated by collagen synthesis in the reprogrammed cells.

Age is more than just a number.

The researchers sought for alterations in the signs of aging to suggest that the cells had been revived. Dr. Diljeet Gill, a postdoc in Wolf Reik's lab at the Institute who worked on the project as a PhD student, explains: "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."

Researchers looked at a variety of cellular age indicators. The first is the epigenetic clock, which uses chemical markers to signal age across the genome. The transcriptome, or all of the gene readouts produced by the cell, is the second. When compared to reference data sets, the reprogrammed cells matched the profile of cells that were 30 years younger by these two metrics.

The technique's prospective applications are contingent on the cells not just appearing younger, but also operating like youthful cells. Collagen, a substance present in bones, skin, tendons, and ligaments, is produced by fibroblasts and aids tissue structure and wound healing. When compared to control cells that did not go through the reprogramming process, the rejuvenated fibroblasts produced more collagen proteins. Fibroblasts also migrate to places in need of repair. Researchers used an artificial cut in a layer of cells in a dish to test the partially regenerated cells. They discovered that treated fibroblasts moved faster into the gap than older cells. This is an encouraging hint that one day this study will be used to develop cells that are more effective at mending wounds.

The researchers discovered that their technique had an influence on other genes connected to age-related disorders and symptoms, which could lead to new therapeutic possibilities in the future. Both the APBA2 gene, which is linked to Alzheimer's illness, and the MAF gene, which plays a role in cataract formation, revealed young transcription alterations.

The process underpinning successful transitory reprogramming is yet unknown, and it will be the next puzzle piece to solve. Key parts of the genome important in determining cell identity, according to the researchers, may be spared from the reprogramming process.

Diljeet concluded: "Our results represent a big step forward in our understanding of cell reprogramming. 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 ageing indicators in genes associated with diseases is particularly promising for the future of this work."

Professor Wolf Reik, a group leader in the Epigenetics research programme who has recently moved to lead the Altos Labs Cambridge Institute, 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."
 

Wnctimes by Marjorie Farrington

Story Source:

Materials provided by Babraham Institute. Note: Content may be edited for style and length.

Journal Reference:

Diljeet Gill, Aled Parry, Fátima Santos, Hanneke Okkenhaug, Christopher D Todd, Irene Hernando-Herraez, Thomas M Stubbs, Inês Milagre, Wolf Reik. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. eLife, 2022; 11 DOI: 10.7554/eLife.71624

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Babraham Institute. "Old skins cells reprogrammed to regain youthful function: Findings could lead to targeted approach for treating aging.." ScienceDaily. ScienceDaily, 8 April 2022. .