Youthful Function of Old Skin Cells Reprogrammed

Researchers have discovered a new approach that will rejuvenate skin cells. The approach has enabled them to reverse the cellular biological clock by about 30 years based on molecular measures. The cells that were somewhat rejuvenated indicated signs of acting more like cells that were younger in experiments that involved imitating a wound to the skin. The study, still in its early stages, might have indications for regenerative medicine, primarily if it is able to replicate in other types of cells.

The study devised a procedure to “time jump” human skin cells 30 years, which turned back the clock of aging for cells that didn’t lose their specialized function. The work has had the ability to partially restore the behavior of older cells in addition to rejuvenating the molecular measures of biological age. The study while early in exploration, could revolutionize the field of regenerative medicine.

As people age, the function of the cells in our body begin to decline and genome gather aging marks. The goal of regenerative medicine is to replace or repair cells including old ones. An important tool in regenerative biology is the body’s capability to create “induced” stem cells. This process is due to several steps with each deleting a variety of markers that make cells specialized. These cells can possibly turn into any type of cell, but researchers are not able yet to dependently recreate the circumstances that re-differentiate stem cells into all types of cells.

The newest method overcomes the issue of completely deleting the identity of cells by stopping reprogramming part way throughout the process. The team was able to find the perfect balance amid reprogramming cells, thus making them younger biologically yet still able to recapture their specialized objective.

In 2007, the first team turned normal cells which had specific functions into stem cells with specialized capability to develop into any type of cell. The whole process of reprogramming stem cells takes about 50 days utilizing 4 key molecules known as Yamanaka factors. This new method is called “maturation phase transient reprogramming” and exposes cells to the Yamanaka factors for 13 days. Afterwards, changes that are related to aging are eliminated and the cells identity is temporarily lost. The cells that have been partly reprogrammed were allowed time to grow under conditions that were normal to see if their specific function of skin cells (fibroblasts) returned. The results from the genome analysis indicated that cells had retrieved certain markers that were distinctive of skin cells. This was confirmed by observing the production of collagen in the cells that were reprogrammed.

To show the rejuvenation of the cells, the team noticed any changes in aging hallmarks. Their understanding of aging on a molelcular level has advanced over the last few years allowing techniques that scientists can measure age related biological changes in human cells. They had the ability to apply this to their experiment to see if the extent of reprogramming in their new method was achieved.

The team looked at a variety of measures of a cells age. One is the epigenetic clock which is where chemical tags will present throughout the geonome show age. Another is the transcriptome, which is all the gene characteristics which are produced by the cell. Through these measures, the cells that were reprogrammed matched the cell profiles that were 30 years younger when compared to reference data sets.

The possible applications of the method are dependent on the cells not just appearing more youthful, but also functioning like younger cells. Fibroblasts will produce collagen which is a molecule found in skin tendons, bones and ligaments and helps to provide structure for wounds and tissues that are healing. The fibroblasts that were rejuvenated were able to produce extra collagen proteins when compared to controlled cells that didn’t undergo the process of reprogramming.

Fibroblasts will also go into areas that are needing repair. Testing was done on the partially rejuvenated cells through making an artificial cut in cell layers in a dish. They discovered that the treated fibroblasts were able to move into the opening much faster than the old cells. This is an encouraging sign that some day research could create cells that are much better at wound healing.

For the future, the team may find other therapeutic possibilities. They noted that the method can also have an effect on other genes which are related to symptoms and diseases that are age related. The MAF gene plays a role in cataract developmentment, and the APBA2 gene is linked with Alzheimer’s Disease – both indicated changes towards transcription youthful levels.

The mechanism that shows the successful transient reprogramming is not fully understood at this time, and is the next puzzle piece to explore. The team speculates that main areas of the genome which was involved in shaping the identify of the cells might escape the process of reprogramming.

The results show a large step forward to their understanding of reprogramming of cells. They have shown that cells can be rejuvenated and not lose their function and that rejuvenation appears to restore some function to older cells. Observing a reverse in aging indicators in genes linked with diseases is very encouraging for the work’s future.

To view the original scientific study click below:
Multi-omic rejuvenation of human cells by maturation phase transient reprogramming