08 April 2022

Time Jump

Old skin cells were reprogrammed, returning to 30 years ago

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A revolution in regenerative medicine may have been made by researchers from the English Babraham Institute. They have developed a "time jump" method for human skin cells. Scientists expect to "translate the clock" of cell aging for as long as 30 years, and without losing their functions. The work of the researchers made it possible to partially restore the functions of old cells, as well as to rejuvenate the molecular indicators of biological age.

With age, the ability of our cells to function decreases, and traces of aging accumulate in the genome. Regenerative biology is aimed at restoring or replacing cells, including old ones. One of the most important tools of regenerative biology is the ability to create induced pluripotent stem cells (iPSCs). This process is the result of several steps, each of which erases some of the labels that make the cells specialized. Theoretically, these stem cells can become cells of any type, but scientists cannot yet reliably recreate the conditions for the re-differentiation of stem cells into all their types.

The new method is based on the Nobel Prize–winning technology - scientists use it to create iPSCs. This method solves the problem of completely erasing cellular identity by stopping reprogramming in the process. 

The complete process of reprogramming stem cells takes about 50 days using four key molecules called Yamanaki factors – named after the scientist who turned ordinary cells into stem cells for the first time. The new method, called "transient reprogramming of the maturation phase," exposes cells to Yamanaki factors for just 13 days. At this point, age-related changes are removed, and the cells temporarily lose their individuality. The partially reprogrammed cells were given time to grow under normal conditions to see if their specific skin cell function would return. Genome analysis showed that the cells regained markers characteristic of skin cells (fibroblasts), and this was confirmed by the observation of collagen production in reprogrammed cells.

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On the left — fibroblasts of a person 20-22 years old, in the middle — old fibroblasts that have not been reprogrammed, on the right — reprogrammed cells. Collagen is shown in red.

To show that the cells were rejuvenated, the researchers looked for changes in the signs of aging.

"Our understanding of aging at the molecular level has expanded over the past decade, leading to the emergence of methods that allow researchers to measure age-related biological changes in human cells. We were able to apply this in our experiment to determine the degree to which reprogramming of our new method has been achieved," explained Dr. Diljit Gill, one of the researchers, in a press release A jump through time – new technique rewinds the age of skin cells by 30 years

In the future, this research may also open up other therapeutic possibilities.; the researchers noticed that their method also had an effect on other genes associated with age-related diseases and symptoms. The APBA2 gene associated with Alzheimer's disease and the MAF gene, which plays a role in the development of cataracts, showed changes towards the youthful transcription level.

Article by Gill et al. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming is published in the journal eLife – VM.

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