Rejuvenation record
Researchers from the Babraham Institute have developed a method of rejuvenation of human skin cells for 30 years, reversing the biological clock of cells without losing their specialized functions. The work of researchers within the framework of the Institute of Epigenetics program allowed partially restoring the function of old cells, as well as rejuvenating the molecular indicators of biological age. This research is at an early stage, but could revolutionize regenerative medicine.
What is regenerative medicine?
With age, the ability of cells to function decreases, and the genome accumulates signs of aging. Regenerative medicine is aimed at restoring or replacing cells, including old ones. One of the important tools of regenerative biology is the creation of induced pluripotent stem cells. This process consists of several stages, each of which is accompanied by the removal of some labels that make the cells mature, or differentiated. Theoretically, induced stem cells can become cells of any type, but scientists cannot yet reliably recreate the conditions for re-differentiation into all types of cells.
The researchers were looking for a delicate balance in reprogramming, making mature cells biologically younger, and at the same time able to restore their specialized cellular functions.
Turn back the clock
To create young cells from old ones, avoiding the complete erasure of their identity and stopping part of the reprogramming process, the researchers used a method that won the Nobel Prize in 2007: Shinya Yamanaka was the first scientist who turned mature cells with a certain function into stem cells with a special ability to develop into any type of cell. The complete cell reprogramming process takes place in the presence of four key Yamanaka factors and takes about 50 days.
The new method described in this study is called "transitional reprogramming of the maturation phase" (maturation phase transient reprogramming). Cells are exposed to Yamanaki factors 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 specific function would return. Genome analysis showed that the cells restored markers characteristic of skin cells (fibroblasts), and this was confirmed by observing the production of collagen in reprogrammed cells.
Age is not just a number
To show that the cells were rejuvenated, the researchers assessed changes in the signs of aging. Understanding aging at the molecular level has advanced over the past decade, giving rise to methods that allow researchers to measure age-related biological changes in cells. The researchers applied this knowledge in their experiment to determine the degree of rejuvenation.
The researchers used several indicators of cellular age. The first is the epigenetic clock, that is, chemical tags distributed throughout the genome, indicating age. The second is the transcriptome, all gene reads produced by the cell. According to these two indicators, the reprogrammed cells corresponded to the profile of cells that were 30 years younger compared to the control data sets.
The potential applications of this technique are related to the fact that the cells not only look younger, but also function as young. Fibroblasts produce collagen, a protein that supports tissue structure and accelerates wound healing. The rejuvenated fibroblasts produced more collagen compared to the control cells, which were not subjected to the reprogramming process.
Normally, fibroblasts move to areas that need regeneration. The researchers tested partially rejuvenated cells by making an incision in the cell layer in vitro. They found that the rejuvenated fibroblasts move into the artificial wound faster than the old cells. This means that someday this research can be used to create cells that heal skin and other tissues better.
In the future, this work may also open up other possibilities: researchers have noticed that their method affects other genes associated with age-related diseases and symptoms. Thus, the APBA2 gene associated with Alzheimer's disease and the MAF gene, which plays a role in the development of cataracts, showed changes in the direction of youthful transcription levels.
The mechanism underlying successful transient reprogramming is not yet fully understood, and this is the next piece of the puzzle to be solved. The researchers suggest that key regions of the genome involved in the formation of cell identity can avoid the reprogramming process. If they manage to identify genes that rejuvenate without reprogramming, and specifically "tune" them to reduce the effects of aging, the new approach will bring valuable discoveries in the treatment of age-related diseases.
Article D.Gill et al. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming is published in the journal eLife.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Babraham Institute: A jump through time – new technique rewinds the age of skin cells by 30 years.