Old skins cells reprogrammed to regain youthful function
Young fibroblasts in the first image, the two are after 10 days, on the right with treatment, the last two are after 13 days, right with treatment. Red shows collagen production which has been restored. Credit: Fátima Santos, Babraham Institute

The Babraham Institute has developed a method to turn back the clock on human skin cells by 30 years. The Institute's Epigenetics research program has been able to partly restore the function of older cells. This topic is still at an early stage of exploration, but the research published today in the journal eLife could change the way regenerative medicine is practiced.

What is it about medicine that makes it different?

The ability of our cells to function declines as we age. Stem cells can be used to repair or replace old ones. Stem cells are one of the most important tools in regenerative biology. The process is a result of several steps, each of which erases some of the marks that make cells specialized. Stem cells have the potential to become any cell type, but scientists aren't yet able to recreate the conditions to re-differentiate stem cells into all cell types

Time is turning back.

Stem cells can be made using a new method that eliminates the problem of completely wiping out cell identity by stopping part of the way through the process. Researchers were able to find the balance between reprogrammable cells, making them biologically younger, while still being able to regain their specialized cell function.

In 2007, Shinya Yamanaka was the first scientist to turn normal cells into stem cells which can be used to make any cell type. The process of stem cell re-programming can take 50 days. The new method exposes cells to Yamanaka factors in 13 days. The cells have lost their identity after age related changes are removed. The partly reprogrammed cells were given time to grow and see if their function returned. The reprogrammed cells had regained markers that were characteristic of skin cells, and this was confirmed by observing the production of collagen in the reprogrammed cells.

Fibroblast cells migration as part of a wound healing assay. Credit: Fátima Santos, analysis by Hanneke Okkenhaug

The age is not just a number.

The researchers looked for changes in the hallmarks of aging to show that the cells had been rejuvenated. The understanding of aging on a molecular level has progressed over the last decade, giving rise to techniques that allow the study of aging. We were able to apply this to our experiment to determine the extent of the new method achieved.

Researchers looked at different measures of cellular age. The first is the epigenetic clock, where chemical tags are present in the genome. The transcriptome is all the genes produced by the cell. The reprogrammed cells matched the profile of cells that were 30 years younger compared to reference data sets.

The potential applications of this technique are dependent on the functioning of the cells. Fibroblasts help provide structure to tissues and heal wounds. Control cells that did not undergo the process of being reprogrammed produced more of the same type of fibroblasts. Areas that need repairing are where fibroblasts move. Researchers cut a layer of cells in a dish to see if they were rejuvenated. fibroblasts moved into the gap faster than older cells. One day, this research could be used to create cells that are better at healing wounds.

The researchers found that their method had an effect on other genes linked to age-related diseases and symptoms. The APBA2 gene, associated with Alzheimer's disease, and the MAF gene, with a role in the development of cataracts, both showed changes towards youthful levels of transcription.

The mechanism behind the successful Transient Reprogramming is not fully understood, and is the next piece of the puzzle to be explored. Key areas of the genome that are involved in shaping cell identity may escape the process.

Our results represent a big step forward in our understanding of cell reprogrammability. Cells can be rejuvenated without losing their function, and rejuvenation looks to restore some function to old cells. The fact that we saw a reverse of aging indicators in genes associated with diseases is promising for the future of this work.

Professor Wolf Reik, a group leader in the Epigenetics research program who has recently moved to lead the Altos Labs Institute Cambridge, said that the work has very exciting implications. We may be able to identify genes that don't reprogram and target them to reduce the effects of aging. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon.

More information: Multi-omic rejuvenation of human cells by maturation phase transient reprogramming, eLife, 2022. DOI: 10.7554/eLife.71624 Journal information: eLife Citation: Old skin cells reprogrammed to regain youthful function (2022, April 7) retrieved 7 April 2022 from https://phys.org/news/2022-04-skin-cells-reprogrammed-regain-youthful.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.