Ageing of skin cells rewound by 30 years

  • The Babraham Institute has created a new method for rejuvenating skin cells. Researchers were able to reverse the clock of the cellular biological clock for around 30 years using molecular measurements. This is significantly more than any previous reprogramming techniques.
  • In experiments that simulated a skin injury, the partially restored cells displayed signs of being more youthful than their counterparts.
  • Although this research is still in its infancy, it could have potential implications for regenerative medicine if it is replicated in other cell types.

The Babraham Institute’s research has produced a method that ‘time jumps’ human skin cells by thirty years. This reverses the clock of cell aging and does not affect their specialized functions. Researchers from the Institute’s Epigenetics Research Programme have been able partially restore the function and rejuvenate the molecular measurements of biological age. This research was published in the journal and although it is still early in exploration, it could revolutionize regenerative medical care.

What’s regenerative medicine?

As we age, the ability of our cells to function decreases and the genome shows signs of ageing. Regenerative biology is a method of replacing or repairing cells, even old ones. Regenerative biology has one of the most important tools: we can create induced stem cells. This process involves several steps that each erase some of the markings that make cells special. These stem cells could be transformed into any type of cell, although scientists have not yet been able to recreate the conditions that would allow them to do so.

Time travel

This new method is based on the Nobel Prize-winning technique used to make stem cells. It stops reprogramming at the end of the process and completely erases cell identity. Researchers were able to balance the reprogramming of cells to make them more biologically youthful and still regain their specialized cell functions.

Shinya Yamanaka, a scientist who first turned normal cells that have a particular function into stem cells with the ability to grow into any type of cell, was successful in 2007. Stem cell reprogramming can take around 50 days. Four key molecules, called Yamanaka factors, are used. This new method, known as “maturation phase transient programming”, exposes cells for only 13 days to Yamanaka elements. The cells temporarily lose their identity and age-related changes are removed. To determine if their skin cells function had returned, the partially reprogrammed cells were allowed to grow in normal conditions. The genome analysis revealed that the cells had regained skin cell markers (fibroblasts), which was confirmed by collagen production in the reprogrammed tissues.

Age is more than a number

The researchers examined the signs of ageing to determine if the cells had been renewed. Dr Diljeet GILL, , a postdoctoral researcher in Wolf Reik’s lab at the Institute, explained that “Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

Researchers considered multiple measures of cell age. The epigenetic clock is a measure of cellular age that uses chemical tags embedded throughout the genome. The transcriptome is a collection of all gene readouts generated by a cell. These two measures showed that the profile of reprogrammed cells was similar to cells that were 30+ years younger than reference data sets.

This technique has many potential applications. However, the cells must not only appear younger but also function like young cells. Fibroblasts make collagen, which is a molecule that can be found in bones, skin, tendons, and ligaments. This helps to provide structure for tissues and heal wounds. Reprogrammed fibroblasts had more collagen proteins than the control cells. Fibroblasts can also be found in areas that require repair. Researchers created an artificial cut from cells in a dish to test the partially-rejuvenated cells. The researchers found that the treated fibroblasts were able to fill the gap more quickly than older cells. This suggests that this research may one day be used to develop cells that heal wounds better.

This research could open up new therapeutic options in the future. The researchers found that their method had an effect on genes associated with age-related symptoms and diseases. Both the APBA2 genes, which are associated with Alzheimer’s Disease, and the MAF genes that play a role in developing cataracts, showed transcriptional changes toward youthful levels.

It is still unclear what mechanism is behind transient reprogramming’s success. This puzzle will be explored further. Researchers speculate that the reprogramming process might not have affected key parts of the genome that are involved in shaping cells’ identity.

Diljeet concluded that: “Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.”

Professor Wolf Reik was the researcher and said that this research had very exciting implications. “Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon.”


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