Source BABRAHAM INSTITUTE

Translation by Shi Siqian

Edit Wei Xiao

As we age, the function of cells in our body declines and the genome continues to accumulate markers of aging. The purpose of regenerative biology is to repair or replace cells, including senescent cells. One of the most important tools in regenerative biology is the body's ability to generate "induced" stem cells. The process is the result of several steps, each of which erases some of the markers that make the cell specializing. In theory, these stem cells have the potential to become any cell type, but scientists have not been able to stably redifferentiate stem cells into all cell types.

Back in Time

This new approach builds on the Nobel Prize-winning stem cell manufacturing technique by stopping partial reprogramming during stem cell redifferentiation , overcoming the problem that the specificity of cells is completely erased. The method allows researchers to find the precise balance in reprogramming cells to make them biologically younger, while being able to regain their specialized cellular functions.

2007, Shinya Yamanaka(Shinya Yamanaka)For the first time, normal cells with specific functions are turned into stem cells, which have the potential to develop into any cell type. The entire process of stem cell reprogramming, which lasts about 50 days, uses four key molecules called "Yamaka factors." The new method in this study, the "transient reprogramming at maturity" method( maturation phase transient reprogramming), cells only need to be exposed to "Yamaka factor" for 13 days. After 13 days, age-related changes in the cells were removed, temporarily losing functional specificity. To see if skin cell-specific functions were restored, the partially reprogrammed cells were cultured under normal conditions. Genomic analysis revealed that the cells expressed markers specific for skin cells (fibroblasts) after normal culture, while collagen production was also observed in these cells, confirming that these "rejuvenated" cells had regained the properties of skin cells.

Age is more than a number

To demonstrate that these cells had recovered, the researchers looked at changes in hallmarks of aging. Diljeet Gill, a postdoctoral fellow in the laboratory of Professor Wolf Reik, head of the Babraham Institute's Epigenetics Research Program and a doctoral student at the time who was involved in the work, explained: "Over the past decade, our understanding of aging at the molecular level has advanced Many advances have resulted in techniques that allow researchers to measure age-related biological changes in cells. We were able to apply these techniques to our experiments to determine the extent of reprogramming achieved by our new approach." /span>

The researchers looked at various measures of cell age. The first is the epigenetic clock, reflecting age through chemical tags present throughout the genome. The second is the transcriptome, which is the expression of all genes produced by the cell. By these two measures, the reprogrammed cells matched the characteristics of cells 30 years younger than the reference dataset.

The potential application of this technology is in the rejuvenation of cell function, not just looking younger. Fibroblasts (a type of cell in skin tissue that have completed differentiation) produce collagen, a molecule found in bones, skin tendons, and ligaments that helps provide structural support to tissues and heal wounds. The rejuvenated fibroblasts produced more collagen than control cells that had not undergone reprogramming. Fibroblasts also move to areas that need repair. The researchers probed the function of some "age-reversed" cells by making an artificial cut in the cell layer in a petri dish. They found that the treated fibroblasts could enter the gap faster than the old cells. That's a sign that the research could hopefully be applied to create cells that can better heal wounds.

In the future, this research may also open up other therapeutic possibilities. The researchers observed that their approach also had an effect on genes involved in age-related disorders.  APBA2 associated with Alzheimer's disease  Genes and associations with cataract development MAF  ; genes all show transcriptional changes towards young levels.

The mechanism behind successful transient reprogramming is not fully understood, and this is the next piece of the puzzle to explore. The researchers speculate that key regions of the genome involved in shaping a cell's specific identity may escape the reprogramming process.

Diljeet concludes: "Our results represent a major step forward in our understanding of cellular reprogramming. "We've shown that cells can be rejuvenated without losing their function, and in the process can restore some of the functions of differentiated cells. We've also seen a reversal of markers of aging in disease-related genes, a fact that Make the future of this work exciting."

Professor Wolf Reik's recent appointment to the multinational biotech company Altos Labs Cambridge Institute(Altos Labs Cambridge Institute) the person in charge. He said: "This work is very exciting. Ultimately, we may be able to identify genes that 're-youth' cells without reprogramming and specifically target these genes to reduce the effects of aging. This approach has the potential to lead to valuable discoveries that will lead us into a whole new phase of treatment.”

Original link:

https:// www.eurekalert.org/news-releases/948982