Partial cellular reprogramming is a new type of genome editing that aims to rejuvenate cells.
Nanoscience is one of the most promising modern technologies for medical purposes. Genome editing capabilities in particular could prove beneficial for cryonics in the future, which makes it an interesting field of science to follow if you’re interested in cryonics. We at Tomorrow Bio, the first European biotech company specialized in human cryopreservation, certainly are intrigued.
Until now most of the medical progress of nanotechnology came from the reprogramming of stem-cells. For that purpose, scientists revert individual cells back to their most basic form to then give them new attributes. However, this could be made much more efficient through the application of other reprogramming methods.
Now a new approach to this could allow us to rejuvenate tissue without needing to fully reset them to stem cells first: Partial Cellular Reprogramming.
Most cells in our body contain DNA, which is the biological instruction that makes each and every organism on the planet unique (unless you’re an identical twin). The complete set of a person's DNA found in our cells, including every gene can be read out, much like a book. This “script” is called a genome.
Understanding each individual part of the human genome, which consists of around 23.000 genes, would enable us to combat diseases more effectively. Through nanotechnology research we now know that we can revert the state of fully developed cells back to pluripotent, embryonic stem cells by forced overexpression of four specific genes called “Yamanaka Factors”. These are a group of protein transcription factors that play a vital role in induced pluripotent stem cell creation and are therefore often related to longevity research.
By overexpressing these cells they lose all their individual attributes like cellular identity and age and can be repurposed for other means via genome editing. Yet, in some cases, we wouldn’t want the cells to forget their initial purposes.
One of these cases is revival from cryopreservation. Because cells don’t lose their functionality through this process, it would be unnecessary and take a lot of extra time to reset them to stem-cells before rejuvenation. Here, partial cellular reprogramming could be the solution.
If exposed to reprogramming factors for just long enough, it is possible to reverse the age of a cell without erasing its identity, scientists discovered. [1] Halfway to pluripotency, the expression of the YamanakaFactors is stopped, at which point rejuvenation of the cell has taken place, while a reset of its function hasn’t.
Application of this technique proves difficult however. Currently it doesn’t manage to achieve the same levels of cell restoration as a full revert would. If genes are overstimulated for too short, rejuvenation will turn out sub-par. If the factors are overstimulated for too long the cell will forget its identity and purpose (aka. become a stem-cell).
Reprogramming of cells can be divided into three phases: initiation, maturation, and stabilization. [2] Previously, all attempts at partial reprogramming were halted during the initiation phase, as it is the only one that guarantees that no loss of function occurs.
The new technique, recently developed by British scientists, is called maturation phase transient reprogramming (MPTR) as it ventures into the maturation stage, in an attempt to increase revitalization even more.
Previous research shows that full reprogramming can take up to 50 days with current methods. At around day 10 the first substantial benefits to cell health were recorded, while Day 17 usually marks the final day at which reprogramming can still be reversed before cells reach pluripotency.
MPTR used the drug doxycycline to reprogram the Yamanaka Factors, by exposing them to the chemicals for 10, 13, 15 and 17 days respectively, testing for the most effective outcome.
To get the less positive news out of the way first: Some substantial changes to fibroblasts morphology were recorded during reprogramming. Fibroblasts are a type of cell that contributes to the formation of connective tissue and play an important part in the healing of wounds. In cell culture trials this change is not an issue and the cells regain their original shape after the drugs are withdrawn. However, in vivo applications could look less promising. To guarantee cell health, which is the main focus of these trials, more research has to be done.
Additionally, shortening of telomeres, a symptom of cellular aging, was not treated by partial reprogramming. Full reprogramming has previously shown success in extending telomeres.
On the upside: Age reversal of cells was substantial. An average age reduction of 30 years (according to the horvath epigenetic clock) was measured in 25% of reprogrammed cells. Three times more than partial reprogramming techniques that stopped at the initiation stage. At least some age reduction was measured in another 35%. 40% of the results were inconclusive.
The most substantial change was recorded after 13 days of exposure. This might be due to the longer exposure times of 15 and 17 days being stressful for the cell, in turn eating into the rejuvenation gains.
Collagen-production, which usually declines with age, was tested after the trials, to see if the functionality of the cells was kept intact. The tests showed that the rejuvenated cells not only kept their ability to produce collagen, but also produced significantly more, confirming successful rejuvenation.
Genome editing looks to be a promising option aiding in revival from biostasis.
The cryonics industry might reap even more substantial benefits from this new approach, presented by these new studies. Partial cellular reprogramming could allow us to more easily repair cell-damage upon revival from biostasis and even treat the underlying cause of death.
In addition, it could aid in rejuvenating the patients bodies by turning back their biological clocks. This is because cellular recovery is at the forefront of combating death by old age. If individual cells can be made 30 years younger, it is not far-fetched to believe that science will one day figure out how to upscale this process to the entire human organism.
As addressed in a previous article, it is highly unlikely that you would wake up from cryopreservation in an old body. These new research discoveries further support that outlook.
Partial reprogramming has shown to cause cell rejuvenation both in vitro and in vivo. Active clinical use might still be a long way off, but recent studies have taken further steps towards understanding the process of cellular reprogramming. We hope that scientists will eventually be able to perform it safely and efficiently in the future.
This technology, like many nanotechnology approaches, could be used in the treatment of the cause of death of biostasis patients as well as help with future revival and rejuvenation. For that reason, Tomorrow Bio will keep a keen eye on technological progress in this field.
If you are interested in finding out more about cryonics, check out Insight for more articles like this one, or enter your email address below to get one of our newly published ebooks.
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