AgeX Therapeutics has recently published a paper on regenerative medicine: “Toward a unified theory of aging and regeneration.”
https://www.ncbi.nlm.nih.gov/pubmed/31455183
Let’s look under the hood and try to understand their approach. There are generally two types of cells in our bodies, germline and somatic cell. Germline are those types of cells that can essentially live forever. Those cells are in the sperm and egg. When a woman gives birth her germline cells produce a child with no signs of age, despite the fact that the mother is a mature adult.
Somatic cells on the other hand are what makes up our bodies: bones, nerves, blood vessels etc. At AgeX they believe they can reprogram somatic cells into pluripotent germline cells and enable them to regenerate forever.
The basis of their research lies in Antagonistic Pleiotropy, a theory that states that some genes in our DNA code are programmed so that early in our life they are supportive (they aid in cancer prevention) to then later in life have deleterious effects on our bodies (suppressing cancer prevention for example). But the existence of germline cells proves in theory that a cell does not have to age.
AgeX poses a question then: Is it possible to transfer the immortality of germline to somatic cells by reprogramming their DNA?
One gene potentially responsible for aging is the telomerase gene that if reintroduced into somatic cells stops the aging process of the cell altogether. So that would stop the process (but not reverse it).
Human embryos lose natural immortality of cells around week 8 after the egg has been fertilized and after that those cells start to age. So the fundamental question is: can we not only stop aging in a cell but reverse it back to embryonic state.
AgeX claims they are able to do so by nuclear transfer of said cell material into a fresh egg cell.
Their further research leads them to believe that they can also achieve that by using molecules (transcription factors) rather than transplanting it into egg cells.
Their work has been validated with a Horvath clock that measures DNA methylation (reliable metric of biological clock of a cell). They claim they are able to take certain soma cells affected by disease and bring them back to the young stage, resetting their age clock to near 0. They’ve coined this technology Induced Tissue Regeneration (iTX). Their research further expands into the possibility of doing this in-vivo (in live patient).
Dr. Aubrey de Grey VP Of New Technology Discovery at AgeX gives some more details on this in a recent interview with Brent Nally [https://youtu.be/RWRa6kVKv8o?t=1398]
We have two main themes about our work, one is Pure Stem: the lineage committed stem cells that have much higher purity than what anyone else was able to create by a relatively simple but proprietary and extremely effective technology that was pioneered by Dr. Mike West and his team a decade ago that is now moving into clinical trials. The other one is called iTR (induced tissue regeneration) which is essentially a variation on the theme of Induced Pluripotency where people have been trying to figure out how to tweak, titrate the mechanism that Shinya Yamanaka discovered 15 years ago for turning the developmental clock backwards in cells, so that it can be done safely in-vivo (in human body) and at the moment there are promising results from a variety of techniques of doing that. But we believe that it’s still a very high risk strategy because essentially these techniques make cells more stem-like and more undifferentiated so they have a high risk of doing unwanted things to cells that are on the verge of becoming cancerous (of which the body has lots and lots of). So we are developing a variation on that theme that involves different genes that would be manipulated and we believe that those changes will be much safer, much less able to make cells cancerous.
The status of those two projects is not moving very fast (because of lack of funding) but there’s nothing wrong that we’ve encountered; we haven’t hit any technological roadblocks. One thing that’s particularly worth mentioning is we have acquired some technology that we feel is extremely promising in protecting stem cells from the immune system of the recipient which of course is an issue that has beset regenerative medicine since its beginnings. There's a very sharp divide between what’s called autologous vs. allogeneic therapies. Autologous therapies are designed using cells that were originally taken from the person they are going to be given back to after some manipulation whereas allogeneic cells come off the shelf from some random person but the downside is that they then invoke an immune response. So the idea is to get the best of both worlds and the technology we are incorporating into Pure Stem seems to be very promising in that regard.
Some of the techniques that AgeX is exploring to do so:
- Molecular methods
- Small molecule strategies of deliveries
- Exosomes (delivering messenger RNA to cells)
Some additional potential benefits of exploring this type of cell regeneration techniques:
- Ability to early detect cancer and also turn it into an ability to turn off regenerative potential of cancer cells (cancer’s hallmark ability to replicate in the host body).
- Scarless wound repair
